PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Li, K.* ; Neumann, K.* ; Duhan, V.* ; Namineni, S.* ; Hansen, A.L.* ; Wartewig, T.* ; Kurgyis, Z.* ; Holm, C.K.* ; Heikenwälder, M. ; Lang, K.S.* ; Ruland, J.*

The uric acid crystal receptor Clec12A potentiates type I interferon responses.

Proc. Natl. Acad. Sci. U.S.A. 116, 18544-18549 (2019)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
The detection of microbes and damaged host cells by the innate immune system is essential for host defense against infection and tissue homeostasis. However, how distinct positive and negative regulatory signals from immune receptors are integrated to tailor specific responses in complex scenarios remains largely undefined. Clec12A is a myeloid cell-expressed inhibitory C-type lectin receptor that can sense cell death under sterile conditions. Clec12A detects uric acid crystals and limits proinflammatory pathways by counteracting the cell-activating spleen tyrosine kinase (Syk). Here, we surprisingly find that Clec12A additionally amplifies type I IFN (IFN-I) responses in vivo and in vitro. Using retinoic acid-inducible gene I (RIG-I) signaling as a model, we demonstrate that monosodium urate (MSU) crystal sensing by Clec12A enhances cytosolic RNA-induced IFN-I production and the subsequent induction of IFN-I-stimulated genes. Mechanistically, Clec12A engages Src kinase to positively regulate the TBK1-IRF3 signaling module. Consistently, Clec12A-deficient mice exhibit reduced IFN-I responses upon lymphocytic choriomeningitis virus (LCMV) infection, which affects the outcomes of these animals in acute and chronic virus infection models. Thus, our results uncover a previously unrecognized connection between an MSU crystal-sensing receptor and the IFN-I response, and they illustrate how the sensing of extracellular damage-associated molecular patterns (DAMPs) can shape the immune response.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
9.580
2.539
14
17
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Clec12a ; Type I Interferon ; C-type Lectin Receptor ; Tbk1-irf3 Signaling ; Lcmv; Pattern-recognition; Tyrosine Kinase; Immunity; Virus; Dcir; Activation; Micl; Identification; Inflammation; Components
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 116, Heft: 37, Seiten: 18544-18549 Artikelnummer: , Supplement: ,
Verlag National Academy of Sciences
Verlagsort 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-502700-003
DOI 10.1073/pnas.1821351116
WOS ID WOS:000485145400060
Scopus ID 85072042081
PubMed ID 31451663
Erfassungsdatum 2019-09-23
[➜Korrektur melden]