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

48 Citations (Scopus)

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<sup>-/-</sup> mice responded to antigen immunization with hyperinflammatory Tcell responses. Furthermore, transfer of CD4<sup>+</sup>CD45RB<sup>hi</sup> Nlrp12<sup>-/-</sup> 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<sup>-/-</sup> 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<sup>-/-</sup> 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

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Interleukin-4
T-Lymphocytes
Atopic Dermatitis
Autoimmune Experimental Encephalomyelitis
Missense Mutation
Ataxia
Colitis
Cellular Immunity
Paralysis
Autoimmune Diseases
Immunization
Fever
Nucleotides
Antigens
Genes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells. / Lukens, John R.; Gurung, Prajwal; Shaw, Patrick J.; Barr, Maggie J.; Zaki, Md Hasan; Brown, Scott A.; Vogel, Peter; Chi, Hongbo; Kanneganti, Thirumala Devi.

In: Immunity, Vol. 42, No. 4, 21.04.2015, p. 654-664.

Research output: Contribution to journalArticle

Lukens, JR, Gurung, P, Shaw, PJ, Barr, MJ, Zaki, MH, Brown, SA, Vogel, P, Chi, H & Kanneganti, TD 2015, 'The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells', Immunity, vol. 42, no. 4, pp. 654-664. https://doi.org/10.1016/j.immuni.2015.03.006
Lukens, John R. ; Gurung, Prajwal ; Shaw, Patrick J. ; Barr, Maggie J. ; Zaki, Md Hasan ; Brown, Scott A. ; Vogel, Peter ; Chi, Hongbo ; Kanneganti, Thirumala Devi. / The NLRP12 Sensor Negatively Regulates Autoinflammatory Disease by Modulating Interleukin-4 Production in T Cells. In: Immunity. 2015 ; Vol. 42, No. 4. pp. 654-664.
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