期刊
IMMUNITY
卷 42, 期 4, 页码 654-664出版社
CELL PRESS
DOI: 10.1016/j.immuni.2015.03.006
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资金
- St. Jude Children's Research Hospital
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [AR056296]
- National Cancer Institute, part of the NIH [CA163507]
- National Institute of Allergy and Infectious Diseases, NIH [AI101935]
- ALSAC
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 T cell responses. Nlrp12(-/-) mice responded to antigen immunization with hyperinflammatory T cell responses. Furthermore, transfer of CD4(+)CD45RB(hi) Nlrp12(-/-) T cells 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-kappa B regulation and IL-4 production as key mediators of NLRP12-associated disease.
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