Regulatory T cells turn pathogenic

Abstract

Foxp3(+) regulatory T (Treg) cells are considered a sub-lineage of CD4(+) T cells that are protective against autoimmunity due to their essential roles in maintaining immune homeostasis and self-tolerance. However, Treg cells are unstable in vivo in terms of lineage specialization and suppressive function. These unstable Treg cells play roles in the pathogenesis of diseases, which cause safety concerns regarding human Treg cell therapy. In this review, we highlight recent findings that demonstrate the pathogenic conversion of Treg cells in different disease models.

Figure 1

The multilayer feed-forward loop model of autoimmune diseases. (1) Exposed autoantigens and pro-inflammatory cytokines in damaged tissues activate effector Th cells, which in turn exacerbate self-tissue damage. (2) Exposed self-antigens and pro-inflammatory cytokines in damaged tissues promote the generation of exTreg cells, which are pathogenic for the self-tissues. (3) exTreg cells favor the activation and expansion of autoreactive effector Th cells, which may further induce the generation and effector Th-like functions of exTreg cells through Th-producing cytokines. Together, these feed-forward loops constitute a higher-level feed-forward loop (4) that drives the development of autoimmune diseases forward. Th, T helper; Treg, regulatory T.