FIGURE 4.

T cell differentiation and function within the intestinal lamina propria are regulated by histone modifications. A, JMJD3 H3K27me3 demethylase modulates the differentiation of T-cell subsets. The “?” sign refers to a conflicting study which shows that JMJD3 promotes Th17 differentiation (60). B, During intestinal inflammation, histone lysine methyltransferase G9A restricts TGF-beta-mediated differentiation of Th17 and Treg cells. C, Transcription factor Helios recruits histone deacetylases to suppress IL-2 expression in Tregs, leading to Treg anergy. D, Loss of mechanisms that regulate histone modifications can impact the severity of colitis. Loss of JMJD3 caused less severe colitis in mice, whereas depletion of G9A protects against severe colitis. Loss of Helios leads to increased IL-2 expression in Tregs and loss of anergy, in addition to more severe colitis in mice. Supporting references are in brackets. JMJD3-Jumonji domain-containing protein 3.