Role of single-immunoglobulin interleukin-1 related receptor (SIGIRR) in psoriasis

Single-immunoglobulin interleukin-1 related receptor (SIGIRR), also known as Toll/interleukin-1 receptor 8 (TIR-8), is a member of TIR domain–containing family of receptors. It was first characterized as an inhibitor of interleukin-1 receptor (IL-1R) and Toll-like receptor (TLR) signalling. Interleukin (IL)-1 family comprises 11 members that takes part in the inflammatory process and recent evidences have showed a possible role in psoriasis. The purpose of this study was to investigate a possible role of SIGIRR in psoriasis pathogenesis. Through quantitative reverse transcription polymerase chain reaction, we found that IL-1 family members gene expression increased in lesional skin of psoriatic subjects whereas SIGIRR levels decreased. On the other hand, after anti-TNFα treatment, SIGIRR levels increased in lesional psoriatic skin whereas IL-1 family members were downregulated. Through immunohistochemical analysis, we also found that SIGIRR was strongly expressed in all epidermal layers of healthy skin but only in the stratum spinosum and the stratum corneum of psoriatic plaques. Moreover, we treated peripheral blood mononuclear cells (PBMC) isolated from healthy donors with TNF-α as well as anti-TNF-α and SIGIRR gene expression was analyzed; SIGIRR was decreased by TNF-α and increased by anti-TNF-α treatment. Our study provides first evidence that SIGIRR is involved in psoriasis and that TNF-α downregulated it, so that the lack of a negative regulation may be at the basis of psoriasis pathogenesis.