title: Interleukin-1 receptor-associated kinase-M suppresses systemic lupus erythematosus.
abstract: OBJECTIVE
  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-lpr/lpr mice and detailed phenotype analysis was performed.
  
  
  RESULTS
  Irak-m deficiency converted the mild autoimmune phenotype of C57BL/6-lpr/lpr 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-lpr/lpr 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.
authors.affiliation: Medizinische Poliklinik, Campus Innenstadt, Klinikum der Universität München - LMU, Germany.
authors.forename: Maciej
authors.initials: M
authors.lastname: Lech
authors.forename: Claudia
authors.initials: C
authors.lastname: Kantner
authors.forename: Onkar P
authors.initials: OP
authors.lastname: Kulkarni
authors.forename: Mi
authors.initials: M
authors.lastname: Ryu
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Vlasova
authors.forename: Jürgen
authors.initials: J
authors.lastname: Heesemann
authors.forename: David
authors.initials: D
authors.lastname: Anz
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Koichi S
authors.initials: KS
authors.lastname: Kobayashi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.forename: Javier
authors.initials: J
authors.lastname: Martin
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008181:Lupus Nephritis / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D053592:Interleukin-1 Receptor-Associated Kinases; C507772:Irak3 protein, mouse