Review: The function of regulatory T cells at the ocular surface

Abstract

Regulatory T cells (Tregs) are critical modulators of immune homeostasis. Tregs maintain peripheral tolerance to self-antigens, thereby preventing autoimmune disease. Furthermore, Tregs suppress excessive immune responses deleterious to the host. Recent research has deepened our understanding of how Tregs function at the ocular surface. This manuscript describes the classification, the immunosuppressive mechanisms, and the phenotypic plasticity of Tregs. We review the contribution of Tregs to ocular surface autoimmune disease, as well as the function of Tregs in allergy and infection at the ocular surface. Finally, we review the role of Tregs in promoting allotolerance in corneal transplantation.

Immune Privilege and Eye-Derived T-Regulatory Cells

“…In fact, Chauhan et al reported that while Treg frequencies remained unchanged, there was a marked decrease in their potential to suppress the effector Th17 cells in a mouse model of DED. This suggests that dysfunction of Tregs can be presumed to be one of the major causes in ocular anterior segment inflammation such as DED [ 90 , 92 ]. It has also been reported that in vitro- expanded Foxp3 + Tregs maintain a normal phenotype and are capable of suppressing immune-mediated ocular surface inflammation in animal models, with in vitro -expanded Tregs able to more efficiently reduce tear cytokine levels and conjunctival cellular infiltration compared to freshly isolated Tregs [ 93 ].…”

Mechanisms of immune regulation and transplantation immunity in corneal transplants

“…Так, Foulsham W. и соавт. провели исследования патологической конверсии Tregs в условиях экспериментальной кератопластики высокого риска с использованием трансгенных мышей FoxP3 -lineage [30]. Результаты показали, что воспалительный процесс в глазу (обычно имеющий место при трансплантации высокого риска) приводил к потере экспрессии FoxP3 этой регуляторной субпопуляцией лимфоцитов с изменением их в exTregs, фенотипически идентичные эффекторным Th1-клеткам, играющим одну из ключевых ролей в отторжении трансплантата.…”

Regulatory T cells promote corneal endothelial cell survival following transplantation via interleukin-10

“…9,10 Substantial progress has been made in determining the mechanisms by which host factors, such as recipient bed vascularity and inflammation, influence the immune response to corneal allografts. 16 Studies performed by our laboratory [17][18][19][20][21][22][23][24] and others [25][26][27] indicate the critical contribution of Foxp3 + Tregs to immune tolerance in the setting of corneal transplantation. 16 Studies performed by our laboratory [17][18][19][20][21][22][23][24] and others [25][26][27] indicate the critical contribution of Foxp3 + Tregs to immune tolerance in the setting of corneal transplantation.…”

“…17,23 The mechanisms by which Tregs exert their immunosuppressive effects remain an area of intense investigation. 18,38 Of note, there is evidence that IL-10 itself provides cytoprotection for hepatocytes, neurons, and brain microvascular endothelial cells. 18,38 Of note, there is evidence that IL-10 itself provides cytoprotection for hepatocytes, neurons, and brain microvascular endothelial cells.…”

“…[31][32][33][34][35][36][37][38] In addition to modulating dendritic cell function, Tregs are known to suppress effector T cells (Teffs) through different mechanisms, including cytolysis, competition for metabolites, and release of soluble immunosuppressive cytokines such as IL-10. 18,38 Of note, there is evidence that IL-10 itself provides cytoprotection for hepatocytes, neurons, and brain microvascular endothelial cells. [39][40][41][42] However, the cytoprotective effects of Tregs or IL-10 on CEnCs have not been previously studied.…”