TY  - JOUR
AB  - The RNA-binding proteins Roquin-1/2 and Regnase-1 exert essential regulation by controlling proinflammatory mRNA expression to prevent autoimmune disease. More recently, inhibition of this post-transcriptional gene regulatory program has been demonstrated to enable enhanced anti-tumor responses by tumor antigen-specific CD8 + T cells. In this review we describe the functions of these RNA-binding proteins and the phenotypes that arise in association with genetic inhibition or inactivation. We discuss how inducible inactivation of the system reprograms CD4 + and CD8 + T cell fates by changing cell metabolism, activation, differentiation or effector/memory decisions. We furthermore outline what we need to know to precisely modulate this system in order to dampen autoimmune reactions or boost the efficacy of adoptively transferred T cells or chimeric antigen receptor (CAR) T cells in cancer immunotherapies.
AU  - Raj, T.
AU  - Negraschus, A.*
AU  - Heissmeyer, V.
C1  - 66976
C2  - 53391
SP  - 159-170
TI  - Roquin-dependent gene regulation in immune-mediated diseases and future therapies.
JO  - Int. Immunol.
VL  - 35
IS  - 4
PY  - 2022
SN  - 0953-8178
ER  - 

TY  - JOUR
AB  - Differential splicing of mRNAs not only enables regulation of gene expression levels, but also ensures a high degree of gene-product diversity. The extent to which splicing of mRNAs is utilized as a mechanism in immune cells has become evident within the last few years. Still, only a few of these mechanisms have been well studied. In this review we discuss some of the best-understood mechanisms, for instance the differential splicing of CD45 in T cells, as well as immunoglobulin genes in B cells. Beyond that we provide general mechanistic insights on how, when and where this process takes place and discuss the current knowledge regarding these topics in immune cells. We also highlight some of the reported links to immune-related diseases, genome-wide sequencing studies that revealed thousands of differentially spliced transcripts, as well as splicing studies on immune cells that remain mechanistically not fully understood. We thereby display potential emerging topics for future studies centered on splicing mechanisms in immune cells.
AU  - Schaub, A.
AU  - Glasmacher, E.
C1  - 51107
C2  - 43092
CY  - Oxford
SP  - 173-181
TI  - Splicing in immune cells - mechanistic insights and emerging topics.
JO  - Int. Immunol.
VL  - 29
IS  - 4
PB  - Oxford Univ Press
PY  - 2017
SN  - 0953-8178
ER  - 

TY  - JOUR
AB  - Dendritic cells (DC) have been shown to express Matrix Metalloproteinase-13 (MMP-13), but little is known about its specific function in DCs and its role in inflammatory conditions. In the present study, we describe a novel role of MMP-13 in regulating the immunostimulatory function of murine DCs through moderating MHC-I surface presentation, endocytosis, and cytokine/chemokine secretion. MMP-13 expression was confirmed in bone marrow-derived DCs at mRNA and protein level and, furthermore, on activity level. Remarkably, LPS treatment strongly enhanced MMP-13 mRNA expression as well as MMP-13 activity, indicating an important role of MMP-13 in inflammatory processes. Functionally, MMP-13 inhibition did not influence DC migratory capacity, while endocytosis of OVA was significantly decreased. Inhibition of MMP-13 lowered the capability of murine DCs to activate CD8(+) T cells, apparently through reducing MHC-I surface presentation. Decreased surface expression of CD11c on DCs, as well as changes in the DC cytokine/chemokine profile after MMP-13 inhibition, emphasize the influence of MMP-13 on DC function. Moreover, T cell targeting cytokines such as IL-12, IL-23, and IL-6 were significantly reduced. Collectively, our data reveal a novel involvement of MMP-13 in regulating DC immunobiology through moderating MHC-I surface presentation, endocytosis, and cytokine/chemokine secretion. Furthermore, the reduced MHC-I surface presentation by DCs resulted in a poor CD8(+) T cell response in vitro. This novel finding indicates that MMP-13 might be a promising target for therapeutic intervention in inflammatory diseases.
AU  - Bartmann, J.
AU  - Frankenberger, M.
AU  - Neurohr, C.*
AU  - Eickelberg, O.
AU  - Nößner, E.
AU  - von Wulffen, W.
C1  - 47990
C2  - 39798
CY  - Oxford
SP  - 473-487
TI  - A novel role of MMP-13 for murine DC function: Its inhibition dampens T cell activation.
JO  - Int. Immunol.
VL  - 28
IS  - 10
PB  - Oxford Univ Press
PY  - 2016
SN  - 0953-8178
ER  - 

TY  - JOUR
AU  - Yu, P.*
AU  - Wellmann, U.*
AU  - Kunder, S.
AU  - Quintanilla-Martinez, L.
AU  - Jennen, L.
AU  - Dear, N.*
AU  - Amann, K.*
AU  - Bauer, S.*
AU  - Winkler, T.H.*
AU  - Wagner, H.*
C1  - 3559
C2  - 23825
SP  - 1211-1219
TI  - Toll-like receptor 9-independent aggraviation of glomerulonnephritis in a novel model of SLE.
JO  - Int. Immunol.
VL  - 18
PY  - 2006
SN  - 0953-8178
ER  - 

TY  - JOUR
AU  - Milani, V.*
AU  - Frankenberger, B.
AU  - Heinz, O.*
AU  - Brandl, A.
AU  - Ruhland, S.C.
AU  - Issels, R.D.
AU  - Nößner, E.
C1  - 1427
C2  - 24197
SP  - 257-268
TI  - Melanoma-associated antigen tyrosinase but not melan-A/MART-1 expression and presentation dissociate during the heat shock response.
JO  - Int. Immunol.
VL  - 17
PY  - 2005
SN  - 0953-8178
ER  -