Ddb1 Is Essential for the Expansion of CD4 + Helper T Cells by Regulating Cell Cycle Progression and Cell Death

Follicular helper T (T ) cells are specialized CD4 helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of T cells is incompletely understood. Here, we reported that Damage-specific DNA binding protein 1 (Ddb1) was required for expan...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in immunology Vol. 12; p. 722273
Main Authors:	Yang, Lingtao, Chen, Wei, Li, Li, Xiao, Yueyue, Fan, Shilin, Zhang, Quan, Xia, Tian, Li, Mengjie, Hong, Yazhen, Zhao, Tongjin, Li, Qiyuan, Liu, Wen-Hsien, Xiao, Nengming
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 30-08-2021
Subjects:	Animals Cell Cycle - genetics Cell Cycle Checkpoints Cell Death Cell Differentiation - genetics Cell Differentiation - immunology Ddb1 DNA Damage DNA damage response DNA-Binding Proteins - genetics follicular helper T cells G2/M arrest Gene Expression Homeostasis humoral immunity Immunology Immunophenotyping Lymphocyte Activation - genetics Lymphocyte Activation - immunology Mice Mice, Knockout T cell differentiation T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - metabolism Tumor Suppressor Protein p53 - metabolism humoral immunity follicular helper T cells DNA damage response G2/M arrest T cell differentiation Th1 Ddb1
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Follicular helper T (T ) cells are specialized CD4 helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of T cells is incompletely understood. Here, we reported that Damage-specific DNA binding protein 1 (Ddb1) was required for expansion of CD4 helper T cells including T and Th1 cells, germinal center response, and antibody response to acute viral infection. deficiency in activated CD4 T cells resulted in cell cycle arrest at G2-M phase and increased cell death, due to accumulation of DNA damage and hyperactivation of ATM/ATR-Chk1 signaling. Moreover, mice with deletion of both and in activated CD4 T cells phenocopied -deficient mice, suggesting that E3 ligase-dependent function of Ddb1 was crucial for genome maintenance and helper T-cell generation. Therefore, our results indicate that Ddb1 is an essential positive regulator in the expansion of CD4 helper T cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Gustavo Javier Martinez, Rosalind Franklin University of Medicine and Science, United States Present address: Tongjin Zhao, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China These authors have contributed equally to this work This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology Reviewed by: Di Yu, University of Queensland, Australia; Dirk Baumjohann, University Hospital Bonn, Germany
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2021.722273