Immunology: A helping hand against autoimmunity

Abstract

The TH17 helper cells of the immune system have a dark side: they mediate autoimmune disorders. Two drugs that prevent the differentiation and activity of these cells might be of therapeutic value.

Figure 1. Effects of digoxin and SR1001 on TH17 cells

On encountering an antigen on the surface of antigen-presenting cells (and in the presence of IL-6 and TGF-β), naive T cells differentiate into TH17 cells. This event is associated with expression of the nuclear receptors RORγt and RORα. These receptors, particularly RORγt, are required for TH17-cell differentiation and for the expression of IL-23R and IL-17a, among other cytokines. Two studies^, show that digoxin and SR1001 bind RORγt, possibly by competing with the natural agonists of these receptors. By inhibiting the recruitment of co-activators and promoting the recruitment of co-repressors, these antagonists reduce RORγt transcriptional activity, TH17-cell differentiation and IL-17 production, and delay the onset and reduce the severity of autoimmune disease in mice.