| First Author | Lin F | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 10 | Pages | eaax1608 |
| PubMed ID | 31633019 | Mgi Jnum | J:288079 |
| Mgi Id | MGI:6415932 | Doi | 10.1126/sciadv.aax1608 |
| Citation | Lin F, et al. (2019) Epigenetic initiation of the TH17 differentiation program is promoted by Cxxc finger protein 1. Sci Adv 5(10):eaax1608 |
| abstractText | IL-6/STAT3 signaling is known to initiate the TH17 differentiation program, but the upstream regulatory mechanisms remain minimally explored. Here, we show that Cxxc finger protein 1 (Cxxc1) promoted the generation of TH17 cells as an epigenetic regulator and prevented their differentiation into Treg cells. Mice with a T cell-specific deletion of Cxxc1 were protected from experimental autoimmune encephalomyelitis and were more susceptible to Citrobacter rodentium infection. Cxxc1 deficiency decreased IL-6Ralpha expression and impeded IL-6/STAT3 signaling, whereas the overexpression of IL-6Ralpha could partially reverse the defects in Cxxc1-deficient TH17 cells in vitro and in vivo. Genome-wide occupancy analysis revealed that Cxxc1 bound to Il6ralpha gene loci by maintaining the appropriate H3K4me3 modification of its promoter. Therefore, these data highlight that Cxxc1 as a key regulator governs the balance between TH17 and Treg cells by controlling the expression of IL-6Ralpha, which affects IL-6/STAT3 signaling and has an impact on TH17-related autoimmune diseases. |
