IL-1 receptor-associated kinase 1 regulates susceptibility to organ-specific autoimmunity

Caishu Deng, Caius Radu, Asim Diab, May F. Tsen, Rehana Hussain, John S. Cowdery, Michael K. Racke, James A. Thomas

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Infections often precede the development of autoimmunity. Correlation between infection with a specific pathogen and a particular autoimmune disease ranges from moderately strong to quite weak. This lack of correspondence suggests that autoimmunity may result from microbial activation of a generic, as opposed to pathogen-specific host-defense response. The Toll-like receptors, essential to host recognition of microbial invasion, signal through a common, highly conserved pathway, activate innate immunity, and control adaptive immune responses. To determine the influence of Toll/IL-1 signaling on the development of autoimmunity, the responses of wild-type (WT) mice and IL-1R-associated kinase 1 (IRAK1)-deficient mice to induction of experimental autoimmune encephalomyelitis were compared. C57BL/6 and B6.IRAK1-deficient mice were immunized with MOG 35-55/CFA or MOG 35-55/CpG DNA/IFA. WT animals developed severe disease, whereas IRAK1-deficient mice were resistant to experimental autoimmune encephalomyelitis, exhibiting little or no CNS inflammation. IRAK1-deficient T cells also displayed impaired Th1 development, particularly during disease induction, despite normal TCR signaling. These results suggest that IRAK1 and the Toll/IL-1 pathway play an essential role in T cell priming, and demonstrate one means through which innate immunity can control subsequent development of autoimmunity. These findings may also help explain the association between antecedent infection and the development or exacerbations of some autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)2833-2842
Number of pages10
JournalJournal of Immunology
Volume170
Issue number6
DOIs
StatePublished - Mar 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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