期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 6, 页码 3337-3346出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300828
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资金
- Science Foundation Ireland [10/YI/B1827]
- National Children's Research Centre
- European Commission
- Ministero Salute
- Ministero Universita e Ricerca
- Science Foundation Ireland (SFI) [10/YI/B1827] Funding Source: Science Foundation Ireland (SFI)
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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