Toll IL-1R8/single Ig IL-1-related receptor regulates psoriasiform inflammation through direct inhibition of innate IL-17A expression by γδ T cells

Shane E. Russell, Anna M. Stefanska, Malgorzata Kubica, Rachel M. Horan, Alberto Mantovani, Cecilia Garlanda, Padraic G. Fallon, Patrick T. Walsh

Research output: Contribution to journalArticle

Abstract

Expression of the orphan receptor Toll IL-1R8/single Ig IL-1-related receptor has been reported to be reduced in the peripheral blood of psoriatic arthritis patients. However whether TIR8/SIGIRR activity plays a specific role in regulating psoriatic inflammation is unknown. We report that Tir8/Sigirr-deficient mice develop more severe psoriatic inflammation in both the chemical (Aldara)- and cytokine (rIL-23)-induced models of psoriasis. Increased disease severity was associated with enhanced infiltration of Vγ4+ γδ T cells that express significantly elevated levels of IL-17A. Critically, we also demonstrate that TIR8/SIGIRR activity directly suppressed innate IL-17A expression by γδ T cells in vitro and in vivo. Importantly, treatment of Tir8/Sigirr-/- mice with an IL-17A neutralization Ab reversed the enhanced disease severity observed in these mice. This study identifies TIR8/SIGIRR as a novel intrinsic negative regulator of innate IL-17A expression and characterizes a novel mechanism involved in the regulation of psoriatic inflammation.

Original languageEnglish
Pages (from-to)3337-3346
Number of pages10
JournalJournal of Immunology
Volume191
Issue number6
DOIs
Publication statusPublished - Sep 15 2013

ASJC Scopus subject areas

  • Immunology

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