T cell receptor signalling in the control of regulatory T cell differentiation and function

Abstract

Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self-tolerance and inflammatory responses. Recent studies have revealed a discrete mode of TCR signaling that regulates Treg cell differentiation, maintenance and function and that impacts on gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of Treg cells in the context of their function in health and disease.

HIF1α and metabolic reprogramming in inflammation

“…Tregs are classified as professional suppressors of varied immune responses and inflammatory processes, and central keepers of self tolerance (76). Tregs functionally oppose Th17 cells by producing the antiinflammatory cytokine IL-10.…”

DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs

“…The ability to form a stable IS is essential for the proper function of Tregs (10,47). IS formation is dependent on TCR/CD3-driven F-actin reorganization (48).…”

“…FOXP3 expression is critical for the survival, maintenance, and function of Tregs (7)(8)(9). TCR signaling is also important for the induction of Foxp3 gene transcription and Treg function (10). FOXP3 is dispensable for Treg development but is crucial for Treg function, as evidenced by the development of severe autoimmunity in patients and mice deficient in FOXP3 (11).…”

Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood

“…It is becoming increasingly appreciated that self-reactive T cells can and do escape clonal deletion (3,4), and the activity of regulatory T cells (Tregs) is required to maintain immune homeostasis in the presence of autoreactive T cells (5)(6)(7). TCR signaling is crucial for Treg development, differentiation, and suppressive function (8). Mutation in several TCR signaling molecules, including Zap70 and LAT, impairs thymic Treg selection and development (9,10).…”