Медицинская иммунология (Aug 2019)
Autoimmune uveitis - risk factors and problems of immunopathogenesis
Abstract
Recent advances in understanding the mechanisms underlying susceptibility to immune-mediated uveitis (IM) and its pathogenesis are presented. Animal models of human uveitis are described in detail, among which the best characterized models of experimental anterior uveitis are endotoxin-induced uveitis and experimental autoimmune anterior uveitis. As a result of these studies, transcription factors such as STAT3, Interferon regulatory factor 4.8 , regulatory proteins - Suppressor of cytokine signaling 1, 3 (SOCS1, SOCS3) and cytokine signaling pathways that regulate the development of IS and may serve as potential therapeutic targets for treatment. Environmental risk factors contributing to the development of IS are characterized. Data are presented on the influence of physical activity, smoking, the state of the intestinal microbiome, and diet on the incidence of IS, and the known and suspected mechanisms of the participation of risk factors in the initiation and pathogenesis of the disease are described. In particular, the results of studies are presented indicating the existence of two main mechanisms of participation of the intestinal microbiome in the development of IS: intestinal microbiome antigens act as triggers for the activation of T cells specific for retinal antigens and the microbiome modulates the balance of effector subpopulations of T lymphocytes (Th1 and Th17) and immunoregulatory subpopulations cells (Treg). It is reported that high levels of expression of ocular proteins (interphotoreceptor retinoid binding protein - IRBP or S-antigen) in the thymus correlated with resistance to the development of EAU, while low levels correlated with susceptibility to uveitis. These seminal studies The pathogenesis of IU has provided an explanation for the selective susceptibility to autoimmune uveitis and suggests that resistance to uveitis is regulated, at least in part, by the ability to maintain central tolerance to retinal autoantigens. Uveitogenic memory T cells have been described to move from the retina and peripheral lymphoid tissues to the bone marrow, remaining there in a quiescent state until re-stimulation, transforming into various subpopulations of effector cells. Analysis of the results of immunological studies on a mouse model of uveitis and peripheral blood of patients with human uveitis revealed the pathogenetic role of Th17 lymphocytes and the transcription activator STAT3 in the development of autoimmune uveitis and the STAT3 signaling protein is a potential therapeutic target for non-infectious uveitis.
