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

Artikel i vetenskaplig tidskrift
Författare E. Shen
Q. Wang
Hardis Rabe
W. Q. Liu
H. Canto
J. W. Leavenworth
Publicerad i Proceedings of the National Academy of Sciences of the United States of America
Volym 115
Nummer/häfte 26
Sidor 6780-6785
ISSN 0027-8424
Publiceringsår 2018
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Sidor 6780-6785
Språk en
Länkar dx.doi.org/10.1073/pnas.1805239115
Ämnesord follicular helper T cells, follicular regulatory T cells, germinal center response, osteopontin, Bcl6 transcription factor, b-lymphocyte differentiation, germinal center, bcl6, mi-2/nurd, mta3, mechanisms, receptor, blimp-1, Science & Technology - Other Topics
Ämneskategorier Klinisk medicin

Sammanfattning

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 Bc16 TF, which helps determine the phenotype and follicular localization of both CD4(+) follicular helper T cells (T-FH) and follicular regulatory T cells (T-FR). Here we show that Bc16-dependent control of follicular T cells is mediated by a complex formed between Bc16 and the Mi-2 beta-nucleosome-remodeling deacetylase complex (Mi-2 beta-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 Bc16 and the NuRD complex that together regulate the genetic program of both T-FH and T-FR cells. Defective assembly of the Bc16-NuRD complex distorts follicular T cell differentiation, resulting in impaired T-FR development and skewing of the T-FH lineage toward a T(H)1-like program that includes expression of Blimp1, Tbet, granzyme B, and IFN gamma. These findings define a core Bc16-directed transcriptional complex that enables CD4(+) follicular T cells to regulate the germinal center response.

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