Abstract
Missense mutations in the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing family of gene 12 (Nlrp12) are associated with periodic fever syndromes and atopic dermatitis in humans. Here, we have demonstrated a crucial role for NLRP12 in negatively regulating pathogenic Tcell responses. Nlrp12-/- mice responded to antigen immunization with hyperinflammatory Tcell responses. Furthermore, transfer of CD4+CD45RBhi Nlrp12-/- Tcells into immunodeficient mice led to more severe colitis and atopic dermatitis. NLRP12 deficiency did not, however, cause exacerbated ascending paralysis during experimental autoimmune encephalomyelitis (EAE); instead, Nlrp12-/- mice developed atypical neuroinflammatory symptoms that were characterized by ataxia and loss of balance. Enhanced T-cell-mediated interleukin-4 (IL-4) production promotes the development of atypical EAE disease in Nlrp12-/- mice. These results define an unexpected role for NLRP12 as an intrinsic negative regulator of T-cell-mediated immunity and identify altered NF-κB regulation and IL-4 production as key mediators of NLRP12-associated disease.
Original language | English (US) |
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Pages (from-to) | 654-664 |
Number of pages | 11 |
Journal | Immunity |
Volume | 42 |
Issue number | 4 |
DOIs | |
State | Published - Apr 21 2015 |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Infectious Diseases