| First Author | Shen E | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 26 | Pages | 6780-6785 |
| PubMed ID | 29891681 | Mgi Jnum | J:263959 |
| Mgi Id | MGI:6164455 | Doi | 10.1073/pnas.1805239115 |
| Citation | Shen E, et al. (2018) Chromatin remodeling by the NuRD complex regulates development of follicular helper and regulatory T cells. Proc Natl Acad Sci U S A 115(26):6780-6785 |
| abstractText | Lineage commitment and differentiation into CD4(+) T cell subsets reflect an interplay between chromatin regulators and transcription factors (TF). Follicular T cell development is regulated by the Bcl6 TF, which helps determine the phenotype and follicular localization of both CD4(+) follicular helper T cells (TFH) and follicular regulatory T cells (TFR). Here we show that Bcl6-dependent control of follicular T cells is mediated by a complex formed between Bcl6 and the Mi-2beta-nucleosome-remodeling deacetylase complex (Mi-2beta-NuRD). Formation of this complex reflects the contribution of the intracellular isoform of osteopontin (OPN-i), which acts as a scaffold to stabilize binding between Bcl6 and the NuRD complex that together regulate the genetic program of both TFH and TFR cells. Defective assembly of the Bcl6-NuRD complex distorts follicular T cell differentiation, resulting in impaired TFR development and skewing of the TFH lineage toward a TH1-like program that includes expression of Blimp1, Tbet, granzyme B, and IFNgamma. These findings define a core Bcl6-directed transcriptional complex that enables CD4(+) follicular T cells to regulate the germinal center response. |
