Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus
In: Annals of the rheumatic diseases, Jg. 70 (2011), Heft 12, S. 2207-2217
Online
academicJournal
- print, 45 ref
Zugriff:
Objectives Interleukin-1 receptor-associated kinase (IRAK)-M suppresses Toll-like receptor (TLR)-mediated activation of innate immunity during infection. A similar role was hypothesised for IRAK-M in autoimmunity. Methods Irak-m-deficient mice were crossed with autoimmune C57BL/6-Ipr/Ipr mice and detailed phenotype analysis was performed. Results Irak-m deficiency converted the mild autoimmune phenotype of C57BL/6-Ipr/Ipr mice into a massive lymphoproliferative syndrome with lethal autoimmune lung disease and lupus nephritis. Irak-m deficiency induced a number of interferon-related genes, cytokines and plasma cell survival factors in spleen cells of these mice. Irak-m-deficient C57BL/6-Ipr/Ipr mice showed expansion of autoreactive T cells, dysfunctional regulatory T cells and plasma cells which was associated with increased lupus autoantibody production. TLR7 antagonism almost completely abrogated this phenotype consistent with IRAK-M-mediated suppression of TLR7 signalling in vitro. Conclusions These data identify a previously unknown function of IRAK-M—namely, suppression of TLR7-mediated autoimmunity—and mutant IRAK-M as a previously unknown genetic risk for murine SLE.
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Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus
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Autor/in / Beteiligte Person: | LECH, Maciej ; KANTNER, Claudia ; MARTIN, Javier ; ANDERS, Hans-Joachim ; KULKARNI, Onkar P ; RYU, Mi ; VLASOVA, Ekaterina ; HEESEMANN, Jurgen ; ANZ, David ; ENDRES, Stefan ; KOBAYASHI, Koichi S ; FLAVELL, Richard A |
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Zeitschrift: | Annals of the rheumatic diseases, Jg. 70 (2011), Heft 12, S. 2207-2217 |
Veröffentlichung: | London: BMJ Publishing Group, 2011 |
Medientyp: | academicJournal |
Umfang: | print, 45 ref |
ISSN: | 0003-4967 (print) |
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