The Chromatin Regulator Mll1 Supports T Follicular Helper Cell Differentiation by Controlling Expression of Bcl6, LEF-1, and TCF-1.

Autor:	Bélanger S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA., Haupt S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA.; Biomedical Sciences Graduate Program, School of Medicine, University of California, San Diego, La Jolla, CA., Faliti CE; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA., Getzler A; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL., Choi J; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA.; Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.; Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea., Diao H; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL., Karunadharma PP; Genomics Core, The Scripps Research Institute, Jupiter, FL., Bild NA; Genomics Core, The Scripps Research Institute, Jupiter, FL., Pipkin ME; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL., Crotty S; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA.; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, La Jolla, CA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2023 Jun 01; Vol. 210 (11), pp. 1752-1760.
DOI:	10.4049/jimmunol.2200927
Abstrakt:	T follicular helper (TFH) cells are essential for developing protective Ab responses following vaccination. Greater understanding of the genetic program leading to TFH differentiation is needed. Chromatin modifications are central in the control of gene expression. However, detailed knowledge of how chromatin regulators (CRs) regulate differentiation of TFH cells is limited. We screened a large short hairpin RNA library targeting all known CRs in mice and identified the histone methyltransferase mixed lineage leukemia 1 (Mll1) as a positive regulator of TFH differentiation. Loss of Mll1 expression reduced formation of TFH cells following acute viral infection or protein immunization. In addition, expression of the TFH lineage-defining transcription factor Bcl6 was reduced in the absence of Mll1. Transcriptomics analysis identified Lef1 and Tcf7 as genes dependent on Mll1 for their expression, which provides one mechanism for the regulation of TFH differentiation by Mll1. Taken together, CRs such as Mll1 substantially influence TFH differentiation. (Copyright © 2023 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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