Expression of IL-7 receptor on Th1, Th17 lymphocytes in patients with psoriatic arthritis

Abstract

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease of the joints, spine, and entheses that can occur in patients with psoriasis. The prevalence of psoriatic arthritis is high in Russia, in recent years there has been an increase in its incidence rates. The pathogenesis of PsA is based on the activation of Th1, Th17 cells. Pro-inflammatory cytokines produced by the cells are involved in the cascade of reactions leading to the joint deformity and bone destruction. For some autoimmune diseases associated with the Th1/Th17 response, IL-7 has been found to be involved in pathogenetic mechanisms. At the same time, IL-7 is assumed to support autoreactive T lymphocytes. Effect of the cytokine on cells is provided by the binding to a specific receptor thus causing a signal transmission into the cell and inducing the processes of differentiation, proliferation, and production of cytokines. In animal models of autoimmune diseases, usage of blocking antibodies to α-chain of the IL-7 receptor (IL-7R) was shown to cause reduced inflammation in target tissues and decreased number of infiltrating T lymphocytes. Therefore, the aim of this work was to investigate the in vitro effects of IL-7 and blockade of the α-chain of the IL-7 receptor on the contents of Th1, Th17 lymphocytes and expression of IL-7 receptor subunits on these cells in normal subjects and in psoriatic arthritis. The study included nine patients with PsA in the stage of exacerbation of the underlying disease (mean age 44±6.5 years) and 6 healthy individuals (mean age 45±2.7 years). The in vitro effects of IL-7 and specific blocking monoclonal antibodies (aCD127) was evaluated in cultures of mononuclear cells from peripheral blood. Flow cytometry was used to determine the expression of IL-7 receptor subunits (CD127, CD132) and to assess cell phenotypes in peripheral blood and cultured cells. We have shown for the first time that patients with PsA have an increased number of CD127+CD132- and CD127+CD132+ cells among Th17 lymphocytes, as well as CD127+CD132-, CD127+CD132+ and CD127-CD132+ cells among Th1 lymphocytes, which suggests participation of IL-7 in maintaining these cell populations. Upon the in vitro supplement of IL-7, an increase in the Th1 cell contents and a decreased number of Th17 cells were observed, both in donors and PsA patients, and the opposite effect was observed under the conditions of IL-7R of blockade. Under the influence of IL-7, as well as with blocking antibodies, there was a significant decrease in CD127 expression on Th1, Th17 lymphocytes. However, a decrease in the number of CD127-132+ among Th1, Th17 lymphocytes occurred only following blockade with antibodies. That is, despite redistribution of Th1 and Th17 lymphocytes in culture, the cells of these populations were not activated under the IL-7 receptor blockade. The obtained data may serve as a basis for choosing the IL-7 receptor as a target in the development of targeted drugs for the treatment of PsA.