The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells

John R. Lukens, Prajwal Gurung, Patrick J. Shaw, Maggie J. Barr, Md Hasan Zaki, Scott A. Brown, Peter Vogel, Hongbo Chi, Thirumala Devi Kanneganti

Research output: Contribution to journalArticle

55 Scopus citations

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 languageEnglish (US)
Pages (from-to)654-664
Number of pages11
JournalImmunity
Volume42
Issue number4
DOIs
StatePublished - Apr 21 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Lukens, J. R., Gurung, P., Shaw, P. J., Barr, M. J., Zaki, M. H., Brown, S. A., Vogel, P., Chi, H., & Kanneganti, T. D. (2015). The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells. Immunity, 42(4), 654-664. https://doi.org/10.1016/j.immuni.2015.03.006