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Toll IL-1R8/Single Ig IL-1-Related Receptor Regulates Psoriasiform Inflammation through Direct Inhibition of Innate IL-17A Expression by gamma delta T Cells
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/Sigir...
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Published in: | The Journal of immunology (1950) 2013-09, Vol.191 (6), p.3337-3346 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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 V gamma 4+ gamma delta 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 gamma delta 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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ISSN: | 0022-1767 |
DOI: | 10.4049/jimmunol.1300828 |