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Chromatin remodeling by the NuRD complex regulates development of follicular helper and regulatory T cells.


ABSTRACT: 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-2?-nucleosome-remodeling deacetylase complex (Mi-2?-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 IFN?. These findings define a core Bcl6-directed transcriptional complex that enables CD4+ follicular T cells to regulate the germinal center response.

SUBMITTER: Shen E 

PROVIDER: S-EPMC6042103 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Chromatin remodeling by the NuRD complex regulates development of follicular helper and regulatory T cells.

Shen Erxia E   Wang Qin Q   Rabe Hardis H   Liu Wenquan W   Cantor Harvey H   Leavenworth Jianmei W JW  

Proceedings of the National Academy of Sciences of the United States of America 20180611 26


Lineage commitment and differentiation into CD4<sup>+</sup> 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<sup>+</sup> follicular helper T cells (T<sub>FH</sub>) and follicular regulatory T cells (T<sub>FR</sub>). Here we show that Bcl6-dependent control of follicular T cells is mediated by a complex formed betwee  ...[more]

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