TY  - JOUR
AB  - The seeded growth of pathogenic protein aggregates underlies the pathogenesis of Alzheimer's disease (AD), but how this pathological cascade is initiated is not fully understood. Sporadic AD is linked genetically to apolipoprotein E (APOE) and other genes expressed in microglia related to immune, lipid, and endocytic functions. We generated a transgenic knockin mouse expressing HaloTag-tagged APOE and optimized experimental protocols for the biochemical purification of APOE, which enabled us to identify fibrillary aggregates of APOE in mice with amyloid-β (Aβ) amyloidosis and in human AD brain autopsies. These APOE aggregates that stained positive for β sheet-binding dyes triggered Aβ amyloidosis within the endo-lysosomal system of microglia, in a process influenced by microglial lipid metabolism and the JAK/STAT signaling pathway. Taking these observations together, we propose a model for the onset of Aβ amyloidosis in AD, suggesting that the endocytic uptake and aggregation of APOE by microglia can initiate Aβ plaque formation.
AU  - Kaji, S.*
AU  - Berghoff, S.A.*
AU  - Spieth, L.*
AU  - Schlaphoff, L.*
AU  - Sasmita, A.O.*
AU  - Vitale, S.*
AU  - Büschgens, L.*
AU  - Kedia, S.*
AU  - Zirngibl, M.*
AU  - Nazarenko, T.*
AU  - Damkou, A.*
AU  - Hosang, L.*
AU  - Depp, C.*
AU  - Kamp, F.*
AU  - Scholz, P.*
AU  - Ewers, D.*
AU  - Giera, M.*
AU  - Ischebeck, T.*
AU  - Wurst, W.
AU  - Wefers, B.
AU  - Schifferer, M.*
AU  - Willem, M.*
AU  - Nave, K.A.*
AU  - Haass, C.*
AU  - Arzberger, T.*
AU  - Jäkel, S.*
AU  - Wirths, O.*
AU  - Saher, G.*
AU  - Simons, M.*
C1  - 72049
C2  - 56531
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 2651-2668.e12
TI  - Apolipoprotein E aggregation in microglia initiates Alzheimer's disease pathology by seeding β-amyloidosis.
JO  - Immunity
VL  - 57
IS  - 11
PB  - Cell Press
PY  - 2024
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth. Deletion of the IL-22 receptor on cancer cells decreases metastasis to a degree similar to that seen in IL-22-deficient mice. IL-22 induced high expression of CD155, which bound to the activating receptor CD226 on NK cells. Excessive activation led to decreased amounts of CD226 and functionally impaired NK cells, which elevated the metastatic burden. IL-22 signaling was also associated with CD155 expression in human datasets and with poor patient outcomes. Taken together, our findings reveal an immunosuppressive circuit activated by T cell-derived IL-22 that promotes lung metastasis.
AU  - Briukhovetska, D.*
AU  - Suarez-Gosalvez, J.*
AU  - Voigt, C.*
AU  - Markota, A.*
AU  - Giannou, A.D.*
AU  - Schübel, M.*
AU  - Jobst, J.*
AU  - Zhang, T.*
AU  - Dörr, J.*
AU  - Märkl, F.*
AU  - Majed, L.*
AU  - Müller, P.J.*
AU  - May, P.*
AU  - Gottschlich, A.*
AU  - Tokarew, N.*
AU  - Lücke, J.*
AU  - Oner, A.*
AU  - Schwerdtfeger, M.*
AU  - Andreu-Sanz, D.*
AU  - Grünmeier, R.*
AU  - Seifert, M.*
AU  - Michaelides, S.*
AU  - Hristov, M.*
AU  - König, L.M.*
AU  - Cadilha, B.L.*
AU  - Mikhaylov, O.*
AU  - Anders, H.J.*
AU  - Rothenfußer, S.
AU  - Flavell, R.A.*
AU  - Cerezo-Wallis, D.*
AU  - Tejedo, C.*
AU  - Soengas, M.S.*
AU  - Bald, T.*
AU  - Huber, S.*
AU  - Endres, S.
AU  - Kobold, S.
C1  - 67212
C2  - 54223
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 143-161.e11
TI  - T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.
JO  - Immunity
VL  - 56
IS  - 1
PB  - Cell Press
PY  - 2023
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.
AU  - Giannou, A.D.*
AU  - Kempski, J.*
AU  - Shiri, A.M.*
AU  - Lücke, J.*
AU  - Zhang, T.*
AU  - Zhao, L.*
AU  - Zazara, D.E.*
AU  - Cortesi, F.*
AU  - Riecken, K.*
AU  - Amezcua Vesely, M.C.*
AU  - Low, J.S.*
AU  - Xu, H.*
AU  - Kaffe, E.*
AU  - Garcia-Perez, L.*
AU  - Agalioti, T.*
AU  - Yamada, Y.*
AU  - Jungraithmayr, W.*
AU  - Zigmond, E.*
AU  - Karstens, K.F.*
AU  - Steglich, B.*
AU  - Wagner, J.*
AU  - Konczalla, L.*
AU  - Carambia, A.*
AU  - Schulze, K.*
AU  - von Felden, J.*
AU  - May, P.*
AU  - Briukhovetska, D.*
AU  - Bedke, T.*
AU  - Brockmann, L.*
AU  - Starzonek, S.*
AU  - Lange, T.*
AU  - Koch, C.*
AU  - Riethdorf, S.*
AU  - Pelczar, P.*
AU  - Böttcher, M.*
AU  - Sabihi, M.*
AU  - Huber, F.J.*
AU  - Reeh, M.*
AU  - Grass, J.K.*
AU  - Wahib, R.*
AU  - Seese, H.*
AU  - Stüben, B.O.*
AU  - Fard-Aghaie, M.*
AU  - Duprée, A.*
AU  - Scognamiglio, P.*
AU  - Plitzko, G.*
AU  - Meiners, J.*
AU  - Soukou, S.*
AU  - Wittek, A.*
AU  - Manthey, C.*
AU  - Maroulis, I.C.*
AU  - Arck, P.C.*
AU  - Perez, D.*
AU  - Gao, B.*
AU  - Zarogiannis, S.G.*
AU  - Strowig, T.*
AU  - Pasqualini, R.*
AU  - Arap, W.*
AU  - Gosálvez, J.S.*
AU  - Kobold, S.
AU  - Prinz, I.*
AU  - Guse, A.H.*
AU  - Tachezy, M.*
AU  - Ghadban, T.*
AU  - Heumann, A.*
AU  - Li, J.*
AU  - Melling, N.*
AU  - Mann, O.*
AU  - Izbicki, J.R.*
AU  - Pantel, K.*
AU  - Schumacher, U.*
AU  - Lohse, A.W.*
AU  - Flavell, R.A.*
AU  - Gagliani, N.*
AU  - Huber, S.*
C1  - 67213
C2  - 54224
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 125-142.e12
TI  - Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.
JO  - Immunity
VL  - 56
IS  - 1
PB  - Cell Press
PY  - 2023
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - It is currently not well known how necroptosis and necroptosis responses manifest in vivo. Here, we uncovered a molecular switch facilitating reprogramming between two alternative modes of necroptosis signaling in hepatocytes, fundamentally affecting immune responses and hepatocarcinogenesis. Concomitant necrosome and NF-κB activation in hepatocytes, which physiologically express low concentrations of receptor-interacting kinase 3 (RIPK3), did not lead to immediate cell death but forced them into a prolonged “sublethal” state with leaky membranes, functioning as secretory cells that released specific chemokines including CCL20 and MCP-1. This triggered hepatic cell proliferation as well as activation of procarcinogenic monocyte-derived macrophage cell clusters, contributing to hepatocarcinogenesis. In contrast, necrosome activation in hepatocytes with inactive NF-κB-signaling caused an accelerated execution of necroptosis, limiting alarmin release, and thereby preventing inflammation and hepatocarcinogenesis. Consistently, intratumoral NF-κB-necroptosis signatures were associated with poor prognosis in human hepatocarcinogenesis. Therefore, pharmacological reprogramming between these distinct forms of necroptosis may represent a promising strategy against hepatocellular carcinoma.
AU  - Vucur, M.*
AU  - Ghallab, A.*
AU  - Schneider, A.T.*
AU  - Adili, A.*
AU  - Cheng, M.*
AU  - Castoldi, M.*
AU  - Singer, M.T.*
AU  - Büttner, V.*
AU  - Keysberg, L.S.*
AU  - Küsgens, L.*
AU  - Kohlhepp, M.*
AU  - Görg, B.*
AU  - Gallage, S.*
AU  - Barragan Avila, J.E.*
AU  - Unger, K.
AU  - Kordes, C.*
AU  - Leblond, A.L.*
AU  - Albrecht, W.*
AU  - Loosen, S.H.*
AU  - Lohr, C.*
AU  - Jördens, M.S.*
AU  - Babler, A.*
AU  - Hayat, S.*
AU  - Schumacher, D.*
AU  - Koenen, M.T.*
AU  - Govaere, O.*
AU  - Boekschoten, M.V.*
AU  - Jors, S.*
AU  - Villacorta-Martin, C.*
AU  - Mazzaferro, V.*
AU  - Llovet, J.M.*
AU  - Weiskirchen, R.*
AU  - Kather, J.N.*
AU  - Starlinger, P.*
AU  - Trauner, M.*
AU  - Luedde, M.*
AU  - Heij, L.R.*
AU  - Neumann, U.P.*
AU  - Keitel, V.*
AU  - Bode, J.G.*
AU  - Schneider, R.K.*
AU  - Tacke, F.*
AU  - Levkau, B.*
AU  - Lammers, T.*
AU  - Fluegen, G.*
AU  - Alexandrov, T.*
AU  - Collins, A.L.*
AU  - Nelson, G.*
AU  - Oakley, F.*
AU  - Mann, D.A.*
AU  - Roderburg, C.*
AU  - Longerich, T.*
AU  - Weber, A.*
AU  - Villanueva, A.*
AU  - Samson, A.L.*
AU  - Murphy, J.M.*
AU  - Kramann, R.*
AU  - Geisler, F.*
AU  - Costa, I.G.*
AU  - Hengstler, J.G.*
AU  - Heikenwälder, M.*
AU  - Luedde, T.*
C1  - 68415
C2  - 54679
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 1578-1595.e8
TI  - Sublethal necroptosis signaling promotes inflammation and liver cancer.
JO  - Immunity
VL  - 56
IS  - 7
PB  - Cell Press
PY  - 2023
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils "plucked" intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events.
AU  - Petzold, T.*
AU  - Zhang, Z.*
AU  - Ballesteros, I.*
AU  - Saleh, I.*
AU  - Polzin, A.*
AU  - Thienel, M.*
AU  - Liu, L.*
AU  - Ul Ain, Q.*
AU  - Ehreiser, V.*
AU  - Weber, C.*
AU  - Kilani, B.*
AU  - Mertsch, P.*
AU  - Götschke, J.*
AU  - Cremer, S.*
AU  - Fu, W.*
AU  - Lorenz, M.*
AU  - Ishikawa-Ankerhold, H.*
AU  - Raatz, E.*
AU  - El-Nemr, S.*
AU  - Görlach, A.*
AU  - Marhuenda, E.*
AU  - Stark, K.*
AU  - Pircher, J.*
AU  - Stegner, D.*
AU  - Gieger, C.
AU  - Schmidt-Supprian, M.*
AU  - Gaertner, F.C.*
AU  - Almendros, I.*
AU  - Kelm, M.*
AU  - Schulz, C.*
AU  - Hidalgo, A.*
AU  - Massberg, S.*
C1  - 66465
C2  - 52840
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 2285-2299.e7
TI  - Neutrophil "plucking" on megakaryocytes drives platelet production and boosts cardiovascular disease.
JO  - Immunity
VL  - 55
IS  - 12
PB  - Cell Press
PY  - 2022
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Innate-like T cell populations expressing conserved TCRs play critical roles in immunity through diverse developmentally acquired effector functions. Focusing on the prototypical lineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanisms and timing of fate decisions and functional effector differentiation. Utilizing induced expression of the semi-invariant NKT cell TCR on double positive thymocytes, an initially highly synchronous wave of iNKT cell development was triggered by brief homogeneous TCR signaling. After reaching a uniform progenitor state characterized by IL-4 production potential and proliferation, effector subsets emerged simultaneously, but then diverged toward different fates. While NKT17 specification was quickly completed, NKT1 cells slowly differentiated and expanded. NKT2 cells resembled maturing progenitors, which gradually diminished in numbers. Thus, iNKT subset diversification occurs in dividing progenitor cells without acute TCR input but utilizes multiple active cytokine signaling pathways. These data imply a two-step model of iNKT effector differentiation.
AU  - Bortoluzzi, S.*
AU  - Dashtsoodol, N.*
AU  - Engleitner, T.*
AU  - Drees, C.*
AU  - Helmrath, S.*
AU  - Mir, J.*
AU  - Toska, A.*
AU  - Flossdorf, M.*
AU  - Öllinger, R.*
AU  - Solovey, M.
AU  - Colomé-Tatché, M.
AU  - Kalfaoglu, B.*
AU  - Ono, M.*
AU  - Buch, T.*
AU  - Ammon, T.*
AU  - Rad, R.*
AU  - Schmidt-Supprian, M.*
C1  - 63110
C2  - 51314
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 2497-2513.e9
TI  - Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling.
JO  - Immunity
VL  - 54
IS  - 11
PB  - Cell Press
PY  - 2021
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - In this issue of Immunity, Britton et al. (2019) demonstrate that the colonization of germ-free mice with microbiotas from inflammatory bowel disease patients induces an altered ratio of ROR gamma t(+) regulatory T cells to T(h17) effector cells and recapitulates human disease severity in colitis-susceptible mice.
AU  - de Jong, R.J.
AU  - Ohnmacht, C.
C1  - 55101
C2  - 46324
CY  - 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
SP  - 8-10
TI  - Defining dysbiosis in inflammatory bowel disease.
JO  - Immunity
VL  - 50
IS  - 1
PB  - Cell Press
PY  - 2019
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - B lymphocytes can suppress immunity through interleukin (IL)-10 production in infectious, autoimmune, and malignant diseases. Here, we have identified a natural plasma cell subset that distinctively expresses the inhibitory receptor LAG-3 and mediates this function in vivo. These plasma cells also express the inhibitory receptors CD200, PD-L1, and PD-L2. They develop from various B cell subsets in a B cell receptor (BCR)-dependent manner independently of microbiota in naive mice. After challenge they upregulate IL-10 expression via a Toll-like receptor-driven mechanism within hours and without proliferating. This function is associated with a unique transcriptome and epigenome, including the lowest amount of DNA methylation at the Il10 locus compared to other B cell subsets. Their augmented accumulation in naive mutant mice with increased BCR signaling correlates with the inhibition of memory T cell formation and vaccine efficacy after challenge. These natural regulatory plasma cells may be of broad relevance for disease intervention.
AU  - Lino, A.C.*
AU  - Dang, V.D.*
AU  - Lampropoulou, V.*
AU  - Welle, A.*
AU  - Joedicke, J.*
AU  - Pohar, J.*
AU  - Simon, Q.*
AU  - Thalmensi, J.*
AU  - Baures, A.*
AU  - Flühler, V.*
AU  - Sakwa, I.*
AU  - Stervbo, U.*
AU  - Ries, S.*
AU  - Jouneau, L.*
AU  - Boudinot, P.*
AU  - Tsubata, T.*
AU  - Adachi, T.*
AU  - Hutloff, A.*
AU  - Dörner, T.*
AU  - Zimber-Strobl, U.
AU  - de Vos, A.F.*
AU  - Dahlke, K.*
AU  - Loh, G.*
AU  - Korniotis, S.*
AU  - Goosmann, C.*
AU  - Weill, J.C.*
AU  - Reynaud, C.A.*
AU  - Kaufmann, S.H.E.*
AU  - Walter, J.*
AU  - Fillatreau, S.*
C1  - 53910
C2  - 45096
SP  - 120-133.e9
TI  - LAG-3 inhibitory receptor expression identifies immunosuppressive natural regulatory plasma cells.
JO  - Immunity
VL  - 49
IS  - 1
PY  - 2018
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17 92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhan ced Akt-mTOR signaling and protein synthesis, whereas inhibition of PI3K or mTOR in Roquin-deficient T cells corrected enhanced Tfh and Th17 or reduced iTreg cell differentiation. Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells. Essig et al. show that spontaneous activation and aberrant differentiation of Roquin-deficient T cells involves cell-intrinsic causes in not only conventional T cells but also impaired Treg cell function. In both cell types, Roquin inhibits the PI3K-mTOR signaling pathway at several levels, thereby controlling protein biosynthesis and limiting differentiation toward Th17 and Tfh cells as well as preventing the conversion and functional specialization of Treg into Tfr cells.
AU  - Essig, K.*
AU  - Hu, D.*
AU  - Guimaraes, J.C.*
AU  - Alterauge, D.*
AU  - Edelmann, S.L.
AU  - Raj, T.*
AU  - Kranich, J.*
AU  - Behrens, G.*
AU  - Heiseke, A.F.*
AU  - Floess, S.*
AU  - Klein, J.*
AU  - Maiser, A.*
AU  - Marschall, S.
AU  - Hrabě de Angelis, M.
AU  - Leonhardt, H.*
AU  - Calkhoven, C.F.*
AU  - Nößner, E.
AU  - Brocker, T.*
AU  - Huehn, J.*
AU  - Krug, A.B.*
AU  - Zavolan, M.*
AU  - Baumjohann, D.*
AU  - Heissmeyer, V.
C1  - 52569
C2  - 44061
CY  - Cambridge
SP  - 1067-1082.e12
TI  - Roquin suppresses the PI3K-mTOR signaling pathway to inhibit T helper cell differentiation and conversion of treg to Tfr cells.
JO  - Immunity
VL  - 47
IS  - 6
PB  - Cell Press
PY  - 2017
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Sickness behavior and cognitive dysfunction occur frequently by unknown mechanisms in virus-infected individuals with malignancies treated with type I interferons (IFNs) and in patients with autoimmune disorders. We found that during sickness behavior, single-stranded RNA viruses, double-stranded RNA ligands, and IFNs shared pathways involving engagement of melanoma differentiation-associated protein 5 (MDA5), retinoic acid-inducible gene 1 (RIG-I), and mitochondrial antiviral signaling protein (MAVS), and subsequently induced IFN responses specifically in brain endothelia and epithelia of mice. Behavioral alterations were specifically dependent on brain endothelial and epithelial IFN receptor chain 1 (IFNAR). Using gene profiling, we identified that the endothelia-derived chemokine ligand CXCL10 mediated behavioral changes through impairment of synaptic plasticity. These results identified brain endothelial and epithelial cells as natural gatekeepers for virus-induced sickness behavior, demonstrated tissue specific IFNAR engagement, and established the CXCL10-CXCR3 axis as target for the treatment of behavioral changes during virus infection and type I IFN therapy.
AU  - Blank, T.*
AU  - Detje, C.N.*
AU  - Spieß, A.*
AU  - Hagemeyer, N.*
AU  - Brendecke, S.M.*
AU  - Wolfart, J.*
AU  - Staszewski, O.*
AU  - Zöller, T.*
AU  - Papageorgiou, I.*
AU  - Schneider, J.*
AU  - Paricio-Montesinos, R.*
AU  - Eisel, U.L.*
AU  - Manahan-Vaughan, D.*
AU  - Jansen, S.*
AU  - Lienenklaus, S.*
AU  - Lu, B.*
AU  - Imai, Y.*
AU  - Müller, M.*
AU  - Goelz, S.E.*
AU  - Baker, D.P.*
AU  - Schwaninger, M.*
AU  - Kann, O.*
AU  - Heikenwälder, M.
AU  - Kalinke, U.*
AU  - Prinz, M.*
C1  - 48443
C2  - 41167
CY  - Cambridge
SP  - 901-912
TI  - Brain endothelial- and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment.
JO  - Immunity
VL  - 44
IS  - 4
PB  - Cell Press
PY  - 2016
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Imiquimod is a small-molecule ligand of Toll-like receptor-7 (TLR7) that is licensed for the treatment of viral infections and cancers of the skin. Imiquimod has TLR7-independent activities that are mechanistically unexplained, including NLRP3 inflammasome activation in myeloid cells and apoptosis induction in cancer cells. We investigated the mechanism of inflammasome activation by imiquimod and the related molecule CL097 and determined that K+ efflux was dispensable for NLRP3 activation by these compounds. Imiquimod and CL097 inhibited the quinone oxidoreductases NQO2 and mitochondrial Complex I. This induced a burst of reactive oxygen species (ROS) and thiol oxidation, and led to NLRP3 activation via NEK7, a recently identified component of this inflammasome. Metabolic consequences of Complex I inhibition and endolysosomal effects of imiquimod might also contribute to NLRP3 activation. Our results reveal a K+ efflux-independent mechanism for NLRP3 activation and identify targets of imiquimod that might be clinically relevant.
AU  - Groß, C.*
AU  - Mishra, R.*
AU  - Schneider, K.*
AU  - Médard, G.*
AU  - Wettmarshausen, J.*
AU  - Dittlein, D.
AU  - Shih, H.*
AU  - Gorka, O.*
AU  - König, P.*
AU  - Fromm, S.*
AU  - Magnani, G.*
AU  - Cikovic, T.*
AU  - Hartjes, L.*
AU  - Smollich, J.*
AU  - Robertson, A.A.B.*
AU  - Cooper, M.A.*
AU  - Schmidt-Supprian, M.*
AU  - Schuster, M.*
AU  - Schroder, K.*
AU  - Broz, P.*
AU  - Traidl-Hoffmann, C.
AU  - Beutler, B.*
AU  - Kuster, B.*
AU  - Ruland, J.*
AU  - Schneider, S.*
AU  - Perocchi, F.
AU  - Groß, O.*
C1  - 49726
C2  - 40883
CY  - Cambridge
SP  - 761-773
TI  - K+ efflux-independent NLRP3 inflammasome activation by small molecules targeting mitochondria.
JO  - Immunity
VL  - 45
IS  - 4
PB  - Cell Press
PY  - 2016
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - According to in vitro assays, T cells are thought to kill rapidly and efficiently, but the efficacy and dynamics of cytotoxic T lymphocyte (CTL)-mediated killing of virus-infected cells in vivo remains elusive. We used two-photon microscopy to quantify CTL-mediated killing in mice infected with herpesviruses or poxviruses. On average, one CTL killed 2-16 virus-infected cells per day as determined by real-time imaging and by mathematical modeling. In contrast, upon virus-induced MHC class I downmodulation, CTLs failed to destroy their targets. During killing, CTLs remained migratory and formed motile kinapses rather than static synapses with targets. Viruses encoding the calcium sensor GCaMP6s revealed strong heterogeneity in individual CTL functional capacity. Furthermore, the probability of death of infected cells increased for those contacted by more than two CTLs, indicative of CTL cooperation. Thus, direct visualization of CTLs during killing of virus-infected cells reveals crucial parameters of CD8(+) T cell immunity.
AU  - Halle, S.*
AU  - Keyser, K.A.*
AU  - Stahl, F.R.*
AU  - Busche, A.*
AU  - Marquardt, A.*
AU  - Zheng, X.*
AU  - Galla, M.*
AU  - Heissmeyer, V.
AU  - Heller, K.*
AU  - Boelter, J.*
AU  - Wagner, K.*
AU  - Bischoff, Y.*
AU  - Martens, R.*
AU  - Braun, A.*
AU  - Werth, K.*
AU  - Uvarovskii, A.*
AU  - Kempf, H.*
AU  - Meyer-Hermann, M.*
AU  - Arens, R.*
AU  - Kremer, M.*
AU  - Sutter, G.*
AU  - Messerle, M.*
AU  - Forster, R.*
C1  - 47914
C2  - 39749
CY  - Cambridge
SP  - 233-245
TI  - In vivo killing capacity of cytotoxic T cells is limited and involves dynamic interactions and T cell cooperativity.
JO  - Immunity
VL  - 44
IS  - 2
PB  - Cell Press
PY  - 2016
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe(-/-) mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4(+) T cells, generated CD4(+), CD8(+), T regulatory (Treg) effector and central memory cells, converted naive CD4(+) T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe(-/-)Ltbr(-/-) and to a similar extent in aged Apoe(-/-)Ltbr(fl/fl)Tagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs.
AU  - Hu, D.
AU  - Mohanta, S.K.*
AU  - Yin, C.*
AU  - Peng, L.*
AU  - Ma, Z.*
AU  - Srikakulapu, P.*
AU  - Grassia, G.*
AU  - MacRitchie, N.*
AU  - Dever, G.*
AU  - Gordon, P.M.*
AU  - Burton, F.L.*
AU  - Ialenti, A.*
AU  - Sabir, S.R.*
AU  - McInnes, I.B.*
AU  - Brewer, J.M.*
AU  - Garside, P.*
AU  - Weber, C.*
AU  - Lehmann, T.*
AU  - Teupser, D.*
AU  - Habenicht, L.*
AU  - Beer, M.*
AU  - Grabner, R.*
AU  - Maffia, P.*
AU  - Weih, F.*
AU  - Habenicht, A.J.R.*
C1  - 45332
C2  - 37285
CY  - Cambridge
SP  - 1100-1115
TI  - Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors.
JO  - Immunity
VL  - 42
IS  - 6
PB  - Cell Press
PY  - 2015
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Kvistborg, P.*
AU  - Gouttefangeas, C.*
AU  - Aghaeepour, N.*
AU  - Cazaly, A.*
AU  - Chattopadhyay, P.K.*
AU  - Chan, C.*
AU  - Eckl, J.
AU  - Finak, G.*
AU  - Hadrup, S.R.*
AU  - Maecker, H.T.*
AU  - Maurer, D.*
AU  - Mosmann, T.*
AU  - Qiu, P.*
AU  - Scheuermann, R.H.*
AU  - Welters, M.J.*
AU  - Ferrari, G.*
AU  - Brinkman, R.R.*
AU  - Britten, C.M.*
C1  - 44469
C2  - 36952
CY  - Cambridge
SP  - 591-592
TI  - Thinking outside the gate: Single-cell assessments in multiple dimensions.
JO  - Immunity
VL  - 42
IS  - 4
PB  - Cell Press
PY  - 2015
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - During persistent antigen stimulation, CD8(+) T cells show a gradual decrease in effector function, referred to as exhaustion, which impairs responses in the setting of tumors and infections. Here we demonstrate that the transcription factor NFAT controls the program of T cell exhaustion. When expressed in cells, an engineered form of NFAT1 unable to interact with AP-1 transcription factors diminished T cell receptor (TCR) signaling, increased the expression of inhibitory cell surface receptors, and interfered with the ability of CD8(+) T cells to protect against Listeria infection and attenuate tumor growth in vivo. We defined the genomic regions occupied by endogenous and engineered NFAT1 in primary CD8(+) T cells and showed that genes directly induced by the engineered NFAT1 overlapped with genes expressed in exhausted CD8(+) T cells in vivo. Our data show that NFAT promotes T cell anergy and exhaustion by binding at sites that do not require cooperation with AP-1.
AU  - Martinez, G.J.*
AU  - Pereira, R.M.*
AU  - Äijö, T.*
AU  - Kim, E.Y.*
AU  - Marangoni, F.*
AU  - Pipkin, M.E.*
AU  - Togher, S.*
AU  - Heissmeyer, V.
AU  - Zhang, Y.C.*
AU  - Crotty, S.*
AU  - Lamperti, E.D.*
AU  - Ansel, K.M.*
AU  - Mempel, T.R.*
AU  - Lähdesmäki, H.*
AU  - Hogan, P.G.*
AU  - Rao, A.*
C1  - 43301
C2  - 37264
CY  - Cambridge
SP  - 265–278
TI  - The transcription factor NFAT promotes exhaustion of activated CD8+ T Cells.
JO  - Immunity
VL  - 42
IS  - 2
PB  - Cell Press
PY  - 2015
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Viral infection induces a number of cytokines that shape T cell responses. In this issue of Immunity, Ray et al. (2014) describe how CD4(+) T cells decide on T follicular helper (Tfh) or T helper 1 (Th1) cell skewed gene expression during acute viral infection.
AU  - Edelmann, S.L.
AU  - Heissmeyer, V.
C1  - 30860
C2  - 33996
CY  - Cambridge
SP  - 307-330
TI  - Tfh cell differentiation: Missing stat3 uncovers interferons' interference.
JO  - Immunity
VL  - 40
IS  - 3
PB  - Cell Press
PY  - 2014
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Maintenance of immunological memory has been proposed to rely on stem-cell-like lymphocytes. However, data supporting this hypothesis are focused on the developmental potential of lymphocyte populations and are thus insufficient to establish the functional hallmarks of stemness. Here, we investigated self-renewal capacity and multipotency of individual memory lymphocytes by in vivo fate mapping of CD8(+) T cells and their descendants across three generations of serial single-cell adoptive transfer and infection-driven re-expansion. We found that immune responses derived from single naive T (Tn) cells, single primary, and single secondary central memory T (Tcm) cells reached similar size and phenotypic diversity, were subjected to comparable stochastic variation, and could ultimately reconstitute immunocompetence against an otherwise lethal infection with the bacterial pathogen Listeria monocytogenes. These observations establish that adult tissue stem cells reside within the CD62L(+) Tcm cell compartment and highlight the promising therapeutic potential of this immune cell subset.
AU  - Graef, P.*
AU  - Buchholz, V.R.*
AU  - Stemberger, C.*
AU  - Flossdorf, M.*
AU  - Henkel, L.*
AU  - Schiemann, M.
AU  - Drexler, I.*
AU  - Höfer, T.*
AU  - Riddell, S.R.*
AU  - Busch, D.H.
C1  - 31780
C2  - 34768
SP  - 116-126
TI  - Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8+ central memory T cells.
JO  - Immunity
VL  - 41
IS  - 1
PY  - 2014
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Type I interferon (IFN) is crucial during infection through its antiviral properties and by coordinating the immunocompetent cells involved in antiviral or antibacterial immunity. Type I IFN (IFN-α and IFN-β) is produced after virus or bacteria recognition by cytosolic receptors or membrane-bound TLR receptors following the activation of the transcription factors IRF3 or IRF7. IFN-β production after fungal infection was recently reported, although the underlying mechanism remains controversial. Here we describe that IFN-β production by dendritic cells (DCs) induced by Candida albicans is largely dependent on Dectin-1- and Dectin-2-mediated signaling. Dectin-1-induced IFN-β production required the tyrosine kinase Syk and the transcription factor IRF5. Type I IFN receptor-deficient mice had a lower survival after C. albicans infection, paralleled by defective renal neutrophil infiltration. IFN-β production by renal infiltrating leukocytes was severely reduced in C. albicans-infected mice with Syk-deficient DCs. These data indicate that Dectin-induced IFN-β production by renal DCs is crucial for defense against C. albicans infection.
AU  - Del Fresno, C.*
AU  - Soulat, D.*
AU  - Roth, S.*
AU  - Blazek, K.*
AU  - Udalova, I.*
AU  - Sancho, D.*
AU  - Ruland, J.
AU  - Ardavín, C.*
C1  - 26120
C2  - 32079
CY  - Cambridge
SP  - 1176-1186
TI  - Interferon-β production via Dectin-1-Syk-IRF5 signaling in dendritic cells is crucial for immunity to C. albicans.
JO  - Immunity
VL  - 38
IS  - 6
PB  - Cell Press
PY  - 2013
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Knowledge of the regional tissue distribution of T cell subsets is a prerequisite for understanding protective immunity and the pathophysiology of T cell-mediated diseases. In this issue of Immunity, Sathaliyawala et al. (2012) present a comprehensive human tissue T cell analysis.
AU  - Neuenhahn, M.
AU  - Busch, D.H.
C1  - 22812
C2  - 30944
SP  - 10-12
TI  - Whole-body anatomy of human T cells.
JO  - Immunity
VL  - 38
IS  - 1
PB  - Cell Press
PY  - 2013
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - The Roquin-1 protein binds to messenger RNAs (mRNAs) and regulates gene expression posttranscriptionally. A single point mutation in Roquin-1, but not gene ablation, increases follicular helper T (Tfh) cell numbers and causes lupus-like autoimmune disease in mice. In T cells, we did not identify a unique role for the much lower expressed paralog Roquin-2. However, combined ablation of both genes induced accumulation of T cells with an effector and follicular helper phenotype. We showed that Roquin-1 and Roquin-2 proteins redundantly repressed the mRNA of inducible costimulator (Icos) and identified the Ox40 costimulatory receptor as another shared mRNA target. Combined acute deletion increased Ox40 signaling, as well as Irf4 expression, and imposed Tfh differentiation on CD4+ T cells. These data imply that both proteins maintain tolerance by preventing inappropriate T cell activation and Tfh cell differentiation, and that Roquin-2 compensates in the absence of Roquin-1, but not in the presence of its mutated form.
AU  - Vogel, K.U.
AU  - Edelmann, S.L.
AU  - Jeltsch, K.
AU  - Bertossi, A.*
AU  - Heger, K.*
AU  - Heinz, G.A.
AU  - Zöller, J.
AU  - Warth, S.C.
AU  - Hoefig, K.P.
AU  - Lohs, C.
AU  - Neff, F.
AU  - Kremmer, E.
AU  - Schick, J.
AU  - Repsilber, D.*
AU  - Geerlof, A.
AU  - Blum, H.*
AU  - Wurst, W.
AU  - Heikenwälder, M.
AU  - Schmidt-Supprian, M.*
AU  - Heissmeyer, V.
C1  - 23821
C2  - 31288
CY  - Cambridge
SP  - 655-668
TI  - Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation.
JO  - Immunity
VL  - 38
IS  - 4
PB  - Cell Press
PY  - 2013
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - C-type lectin receptors (CLRs) that couple with the kinase Syk are major pattern recognition receptors for the activation of innate immunity and host defense. CLRs recognize fungi and other forms of microbial or sterile danger, and they induce inflammatory responses through the adaptor protein Card9. The mechanisms relaying CLR proximal signals to the core Card9 module are unknown. Here we demonstrated that protein kinase C-δ (PKCδ) was activated upon Dectin-1-Syk signaling, mediated phosphorylation of Card9 at Thr231, and was responsible for Card9-Bcl10 complex assembly and canonical NF-κB control. Prkcd(-/-) dendritic cells, but not those lacking PKCα, PKCβ, or PKCθ, were defective in innate responses to Dectin-1, Dectin-2, or Mincle stimulation. Moreover, Candida albicans-induced cytokine production was blocked in Prkcd(-/-) cells, and Prkcd(-/-) mice were highly susceptible to fungal infection. Thus, PKCδ is an essential link between Syk activation and Card9 signaling for CLR-mediated innate immunity and host protection.
AU  - Strasser, D.
AU  - Neumann, K.*
AU  - Bergmann, H.*
AU  - Marakalala, M.J.*
AU  - Guler, R.*
AU  - Rojowska, A.*
AU  - Hopfner, K.-P.*
AU  - Brombacher, F.*
AU  - Urlaub, H.*
AU  - Baier, G.*
AU  - Brown, G.D.*
AU  - Leitges, M.
AU  - Ruland, J.
C1  - 7192
C2  - 29537
SP  - 32-42
TI  - Syk kinase-coupled C-type lectin receptors engage protein kinase C-δ to elicit Card9 adaptor-mediated innate immunity.
JO  - Immunity
VL  - 36
IS  - 1
PB  - Cell Press
PY  - 2012
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Little is known about mechanisms determining the homeostasis of lymphocytes within lymphoid organs. Applying different mouse models, including conditionally proficient Ccr7 gene-targeted mice, we now show that semimature steady state dendritic cells (sDCs) constitutively trafficking into lymph nodes (LNs) were essential contributors to T cell homeostasis in these organs. sDCs provided vascular endothelial growth factor known to support high endothelial venule formation, thus facilitating enhanced homing of T cells to LNs. The presence of sDCs led to increased CCL21 production in T-zone fibroblastic reticular cells. CCL21 is a ligand for CCR7 known to regulate homing as well as retention of T cells in LNs. In addition, we provide evidence that CCL21 binds to the surface of DCs via its heparin-binding domain, further explaining why T cells leave LNs more rapidly in the absence of sDCs. Together, these data reveal multiple roles for sDCs in regulating T cell homeostasis in LNs.
AU  - Wendland, M.*
AU  - Willenzon, S.*
AU  - Kocks, J.*
AU  - Davalos-Misslitz, A.C.*
AU  - Hammerschmidt, S.I.*
AU  - Schumann, K.*
AU  - Kremmer, E.
AU  - Sixt, M.*
AU  - Hoffmeyer, A.*
AU  - Pabst, O.*
AU  - Forster, R.*
C1  - 8595
C2  - 30199
SP  - 945-957
TI  - Lymph node T cell homeostasis relies on steady state homing of dendritic cells.
JO  - Immunity
VL  - 35
IS  - 6
PB  - Cell Press
PY  - 2012
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Activation of the RIG-I signaling molecule is essential for antiviral immunity but mechanisms downmodulating the response are ill defined. In this issue of Immunity, Rajput et al. (2011) describe caspase-8-mediated RIP1 cleavage as a key step for restricting RIG-I signaling.
AU  - Roth, S.*
AU  - Ruland, J.
C1  - 6350
C2  - 29047
CY  - Cambridge, MA, USA
SP  - 283-285
TI  - Caspase-8: Clipping off RIG-I signaling.
JO  - Immunity
VL  - 34
IS  - 3
PB  - Cell Press
PY  - 2011
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - In this issue of Immunity, Turtle et al. (2009) describe the identification of a distinct CD8(+) memory T cell subset in humans, which could bring us closer to the identification of the enigmatic "memory stem cell."
AU  - Neuenhahn, M.
AU  - Busch, D.H.
C1  - 4178
C2  - 27718
SP  - 702-704
TI  - The quest for CD8⁺ memory stem cells.
JO  - Immunity
VL  - 31
IS  - 5
PB  - Elsevier
PY  - 2010
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Inflammatory diseases at epithelial borders develop from aberrant interactions between resident cells of the tissue and invading immunocytes. Here, we unraveled basic functions of epithelial cells and immune cells and the sequence of their interactions in an inflammatory skin disease. Ubiquitous deficiency of the I?B? protein (Ikba?/?) as well as concomitant deletion of Ikba specifically in keratinocytes and T cells (IkbaK5?/K5? lck?/lck?) resulted in an inflammatory skin phenotype that involved the epithelial compartment and depended on the presence of lymphocytes as well as tumor necrosis factor and lymphotoxin signaling. In contrast, mice with selective ablation of Ikba in keratinocytes or lymphocytes showed inflammation limited to the dermal compartment or a normal skin phenotype, respectively. Targeted deletion of RelA from epidermal keratinocytes completely rescued the inflammatory skin phenotype of Ikba?/? mice. This finding emphasizes the important role of aberrant NF-?B activation in both keratinocytes and lymphocytes in the development of the observed inflammatory skin changes.
AU  - Rebholz, B.*
AU  - Haase, I.*
AU  - Eckelt, B.*
AU  - Paxian, S.*
AU  - Flaig, M.J.*
AU  - Ghoreschi, K.*
AU  - Nedospasov, S.A.*
AU  - Mailhammer, R.
AU  - Debey-Pascher, S.*
AU  - Schultze, J.L.*
AU  - Weindl, G.*
AU  - Förster, I.*
AU  - Huss, R.*
AU  - Stratis, A.*
AU  - Ruzicka, T.*
AU  - Röcken, M.*
AU  - Pfeffer, K.*
AU  - Schmid, R.M.*
AU  - Rupec, R.A.*
C1  - 4017
C2  - 24655
SP  - 296-307
TI  - Crosstalk between keratinocytes and adaptive immune cells in an IkappaBalpha protein-mediated inflammatory disease of the skin.
JO  - Immunity
VL  - 27
IS  - 2
PB  - Cell Press
PY  - 2007
SN  - 1074-7613
ER  - 

TY  - JOUR
AB  - Upon first antigen encounter, naive CD8(+) T cells get activated, clonally expand, and can develop into very distinct subsets, such as short-living effector cells or different memory subpopulations. The origin of subset diversification is currently unknown, but qualitative and quantitative differences in early signals received by individual precursor cells have been suggested as a major determinant. We show that transfer of a single antigen-specific naive T cell into a normal recipient mouse allowed recovery of clonally expanded daughter cells upon immunization. With this experimental approach, we conclusively demonstrated that a wide range of diversity could develop out of a single precursor cell, including different types of effector and memory T cells. Interestingly, single-cell-derived subset diversification resembled that of polyclonal T cell responses in the same individual mouse, although differentiation patterns differed between immunization strategies. These data implicate that subset diversification is both shaped and synchronized during the expansion phase.
AU  - Stemberger, C.
AU  - Huster, K.M.
AU  - Koffler, M.*
AU  - Anderl, F.*
AU  - Schiemann, M.*
AU  - Wagner, H.
AU  - Busch, D.H.
C1  - 4229
C2  - 25029
SP  - 985-997
TI  - A single naïve CD8⁺ T cell precursor can develop into diverse effector and memory subsets.
JO  - Immunity
VL  - 27
IS  - 6
PB  - Cell Press
PY  - 2007
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Anfossi, N.*
AU  - André, P.*
AU  - Guia, S.*
AU  - Falk, C.S.
AU  - Roetynck, S.*
AU  - Stewart, C.A.*
AU  - Breso, V.*
AU  - Frassati, C.*
AU  - Reviron, D.*
AU  - Middleton, D.*
AU  - Ugolini, S.*
C1  - 1551
C2  - 23977
SP  - 331-342
TI  - Human NK cell education by inhibitory receptors for MHC class I.
JO  - Immunity
VL  - 25
PY  - 2006
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Nera, K.-P.*
AU  - Kohonen, P.*
AU  - Narvi, E.*
AU  - Peippo, A.*
AU  - Mustonen, L.*
AU  - Terho, P.*
AU  - Koskela, K.*
AU  - Buerstedde, J.-M.
AU  - Lassila, O.*
C1  - 5770
C2  - 24160
SP  - 283-293
TI  - Loss of Pax5 promotes plasma cell differentiation.
JO  - Immunity
VL  - 24
PY  - 2006
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Neuenhahn, M.*
AU  - Kerksiek, K.M.*
AU  - Nauerth, M.*
AU  - Suhre, M.H.*
AU  - Schiemann, M.
AU  - Gebhardt, F.E.*
AU  - Stemberger, C.*
AU  - Panthel, K.*
AU  - Schröder, S.*
AU  - Chakraborty, T.*
AU  - Jung, S.*
AU  - Hochrein, H.*
AU  - Rüssmann, H.*
AU  - Brocker, T.*
AU  - Busch, D.H.
C1  - 2437
C2  - 24020
SP  - 619-630
TI  - CD8alpha+ dendritic cells are required for efficient entry of listeria monocytogenes into the spleen.
JO  - Immunity
VL  - 25
IS  - 4
PY  - 2006
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Yu, P.
AU  - Constien, R.
AU  - Dear, N.
AU  - Katan, M.
AU  - Hanke, P.
AU  - Bunney, T.D.
AU  - Kunder, S.
AU  - Quintanilla-Martinez, L.
AU  - Huffstadt, U.
AU  - Schröder, A.
AU  - Jones, N.P.
AU  - Peters, T.
AU  - Fuchs, H.
AU  - Hrabě de Angelis, M.
AU  - Nehls, M.
AU  - Grosse, J.
AU  - Wabnitz, P.
AU  - Meyer, T.P.H.
AU  - Yasuda, K.
AU  - Schiemann, M.
AU  - Schneider-Fresenius, C.
AU  - Jagla, W.
AU  - Russ, A.
AU  - Popp, A.
AU  - Josephs, M.
AU  - Marquardt, A.
AU  - Laufs, J.
AU  - Schmittwolf, C.
AU  - Wagner, H.
AU  - Pfeffer, K.
AU  - Mudde, G.C.
C1  - 2029
C2  - 22606
SP  - 451-465
TI  - Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase Cgamma2 that specifically increases external Ca2+ entry.
JO  - Immunity
VL  - 22
PY  - 2005
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Mocikat, R.
AU  - Braumüller, H.*
AU  - Gumy, A.*
AU  - Egeter, O.*
AU  - Ziegler, H.*
AU  - Reusch, U.*
AU  - Bubeck, A.*
AU  - Louis, J.*
AU  - Mailhammer, R.
AU  - Riethmüller, G.*
AU  - Koszinowski, U.*
AU  - Röcken, M.*
C1  - 22387
C2  - 21310
SP  - 561-569
TI  - Natural killer cells activated by MHC class ILow targets prime dentritic cells to induce protective  CD8 T cells responses.
JO  - Immunity
VL  - 19
PY  - 2003
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Flügel, A.*
AU  - Berkowicz, T.*
AU  - Ritter, T.*
AU  - Labeur, M.*
AU  - Jenne, D.*
AU  - Li, Z.*
AU  - Ellwart, J.W.
AU  - Willem, M.*
AU  - Lassmann, H.*
AU  - Wekerle, H.*
C1  - 21766
C2  - 19957
SP  - 547-560
TI  - Migratory Activity and Functional Changes of Green Fluorescent Effector Cells before and during Experimental Autoimmune Encephalomyelitis.
JO  - Immunity
VL  - 14
PY  - 2001
SN  - 1074-7613
ER  - 

TY  - JOUR
AU  - Saura, M.*
AU  - Zaragoza, C.*
AU  - McMillan, A.*
AU  - Quick, R.A.*
AU  - Hohenadl, C.
AU  - Lowenstein, J.M.*
C1  - 20816
C2  - 18883
SP  - 21-28
TI  - An antiviral mechanism of nitric oxide : Inhibition of a viral protease.
JO  - Immunity
VL  - 10
PY  - 1999
SN  - 1074-7613
ER  -