Αρχειοθήκη ιστολογίου

Τετάρτη 7 Μαρτίου 2018

TIGIT expression levels on CD4+ T cells are correlated with disease severity in patients with psoriasis

Summary

Background

T-cell immunoglobulin and ITIM domain (TIGIT), a co-inhibitory receptor, suppresses CD4+ T-cell responses by triggering CD155. TIGIT shifts the balance of cytokines, including interferon (IFN)-γ, interleukin (IL)-10 and IL-17A, and affects the proliferation of CD4+ T cells.

Aim

To investigate TIGIT expression and its effects on CD4+ T-cell function in psoriasis.

Methods

In total, 28 patients with psoriasis vulgaris PV and 14 healthy controls (HCs) were enrolled. TIGIT expression on CD4+ T cells was evaluated by flow cytometry analysis and quantitative real-time PCR. Production of IFN-γ, IL-10 and IL-17 was measured with cytometry bead arrays, while CD4+ T cell proliferation was measured using a permeable assay.

Results

IGIT expression on CD4+ T cells and mRNA level were significantly lower in patients with PV compared with HCs. TIGIT expression was negatively correlated with Psoriasis Area and Severity Index. Activation of TIGIT with recombinant human CD155/Fc protein significantly inhibited psoriatic CD4+ T-cell proliferation, decreased production of IFN-γ and IL-17A, and increased IL-10. After blockade with a functional anti-human TIGIT antibody, TIGIT produced the opposite effect on IFN-γ and IL-17A, but had no significant effect on IL-10 or cell proliferation. Furthermore, the frequency of TIGIT+CD4+ T cells was significantly increased in patients with PV after 2 months of treatment with acitretin, with associated significant changes in IFN-γ, IL-10and IL-17A plasma levels.

Conclusions

Downregulation of TIGIT on CD4+ T cells may contribute to the pathogenesis of psoriasis, and activation of the TIGIT signalling pathway may be a potential therapeutic target.



http://ift.tt/2FnXD3o

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου