Epigenetic activation during T helper 17 cell differentiation is mediated by Tripartite motif containing 28 (original) (raw)

“…Consistent with previous studies highlighting the importance of histone demethylases KDM6A/B in cellular development and disease (45)(46)(47)(48), we here extend previous observations that these enzymes are critical regulators of Th17 development and proinflammatory phenotypes. In murine CD4 + T cells, KDM6B ablation promotes CD4 + T cell differentiation into Th2 and Th17 subsets in small intestine and colon (26,49); however, two other independent studies did not observe this enhanced Th17 differentiation in KDM6B-ablated CD4 + T cells (26,27,38) but showed significant impairment of Th17 differentiation and effector function. One possible explanation for this discrepancy may be related to redundant and compensatory roles of KDM6A and KDM6B in T cell differentiation (50).…”

Section: Discussionmentioning

“…Consistent with previous studies highlighting the importance of histone demethylases KDM6A/B in cellular development and disease (46-49), we here extend previous observations that these enzymes are critical regulators of Th17 development and pro-inflammatory phenotypes. In mouse CD4 + T cells, KDM6B ablation promotes CD4 + T cell differentiation into Th2 and Th17 subsets in small intestine and colon (27, 50), however two other independent studies did not observe this enhanced Th17 differentiation in KDM6B ablated CD4 + T cells (27, 28, 39) but showed significant impairment of Th17 differentiation and effector function. One possible explanation for this discrepancy may be related to redundant and compensatory roles of KDM6A and KDM6B in T-cell differentiation (51).…”

Section: Discussionmentioning

“…Deficiency of Fam64a inhibited Th17 cell differentiation but had no obvious effects on the differentiation of Th1, Th2, or iTreg cells. Some other proteins, such as SOCS3, DUSP2, TRIM28, and PKC-θ, have also been reported to regulate Th17 cell differentiation via modulating STAT3 activity (35)(36)(37)(38). For examples, DUSP2 can mediate STAT3 dephosphorylation and suppress Th17 cell differentiation (35); TRIM28 is recruited to STAT3-occupied genes and mediates epigenetic activation during Th17 cell differentiation (36); PKC-θ can up-regulate STAT3 expression to promote Th17 cell differentiation (37).…”

Section: Discussionmentioning