The role of nuclear receptors in regulation of Th17/Treg biology and its implications for diseases

Abstract

Nuclear receptors in the cell play essential roles in environmental sensing, differentiation, development, homeostasis,and metabolism and are thus highly conserved across multiple species. The anti-inflammatory role of nuclear receptors in immune cells has recently gained recognition. Nuclear receptors play critical roles in both myeloid and lymphoid cells, particularly in helper CD41 T-cell type 17 (Th17) and regulatory T cells (Treg). Th17 and Treg are closely related cell fates that are determined by orchestrated cytokine signaling. Recent studies have emphasized the interactions between nuclear receptors and the known cytokine signals and how such interaction affects Th17/Treg development and function.This review will focus on the most recent discoveries concerning the roles of nuclear receptors in the context of therapeutic applications in autoimmune diseases.

Figure 1.

Schematic illustration of nuclear receptor-mediated Treg/Th17 differentiation: Pointed arrows represent positive regulation and blunt arrows represent negative regulation of the target. If known, specific mechanisms are indicated next to the arrows. Nuclear receptors are indicated in blue circles or boxes. Other transcription factors (non-nuclear receptors) are indicated by green circles. Overlapping nuclear receptors indicate direct physical interactions. Abbreviations: sterol regulatory element binding protein-1 (SREBP-1), liver-X-receptors (LXR), vitamin D receptor (VDR), aryl hydrocarbon receptor (AHR), peroxisome proliferator of activated receptor (PPAR), all-trans retinoic acid receptor (RAR), retinoic acid receptor-related orphan receptor (ROR).