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

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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

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Interleukin-1 Receptors
Interleukin-17
Inflammation
T-Lymphocytes
imiquimod
Psoriatic Arthritis
Psoriasis
Cytokines
Therapeutics

ASJC Scopus subject areas

  • Immunology

Cite this

Toll IL-1R8/single Ig IL-1-related receptor regulates psoriasiform inflammation through direct inhibition of innate IL-17A expression by γδ T cells. / Russell, Shane E.; Stefanska, Anna M.; Kubica, Malgorzata; Horan, Rachel M.; Mantovani, Alberto; Garlanda, Cecilia; Fallon, Padraic G.; Walsh, Patrick T.

In: Journal of Immunology, Vol. 191, No. 6, 15.09.2013, p. 3337-3346.

Research output: Contribution to journalArticle

Russell, Shane E. ; Stefanska, Anna M. ; Kubica, Malgorzata ; Horan, Rachel M. ; Mantovani, Alberto ; Garlanda, Cecilia ; Fallon, Padraic G. ; Walsh, Patrick T. / Toll IL-1R8/single Ig IL-1-related receptor regulates psoriasiform inflammation through direct inhibition of innate IL-17A expression by γδ T cells. In: Journal of Immunology. 2013 ; Vol. 191, No. 6. pp. 3337-3346.
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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.",
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AU - Fallon, Padraic G.

AU - Walsh, Patrick T.

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