The Balance of Th17 versus Treg Cells in Autoimmunity

Abstract

T helper type 17 (Th17) cells and pTreg cells, which share a common precursor cell (the naïve CD4 T cell), require a common tumor growth factor (TGF)-β signal for initial differentiation. However, terminally differentiated cells fulfill opposite functions: Th17 cells cause autoimmunity and inflammation, whereas Treg cells inhibit these phenomena and maintain immune homeostasis. Thus, unraveling the mechanisms that affect the Th17/Treg cell balance is critical if we are to better understand autoimmunity and tolerance. Recent studies have identified many factors that influence this balance; these factors range from signaling pathways triggered by T cell receptors, costimulatory receptors, and cytokines, to various metabolic pathways and the intestinal microbiota. This review article summarizes recent advances in our understanding of the Th17/Treg balance and its implications with respect to autoimmune disease.

Keywords: Foxp3; RORγt; Th17; Treg; autoimmunity; balance.

Figure 1

Signaling pathways of T cell receptor (TCR) and costimulatory signal. Simplified view of signaling pathways through TCR and costimulatory signal. TCR binds to peptide–MHC and CD28 binds to B7.1 or B7.2 on the surface of APC. Signaling pathways ultimately induce activation and survival of T cells.

Figure 2

Contributing factors for reciprocal differentiation of Th17 versus pTreg cells. Differentiation of Th17 and pTreg cells are reciprocally regulated by many contributing factors. Cytokines are the most powerful determinants in the regulation. Other factors including TCR signal, costimulatory signal, metabolism, and microbiota also influence the balance. SFB: segmented filamentous bacteria, SCFA: short chain fatty acid, PSA: polysaccharide A.