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

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

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

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Main Authors: Lingtao Yang, Wei Chen, Li Li, Yueyue Xiao, Shilin Fan, Quan Zhang, Tian Xia, Mengjie Li, Yazhen Hong, Tongjin Zhao, Qiyuan Li, Wen-Hsien Liu, Nengming Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Immunology
Subjects:
Ddb1
follicular helper T cells
humoral immunity
DNA damage response
T cell differentiation
G2/M arrest
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.722273/full
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spelling doaj-4c48cf169b94420cbdcb0bbaae112df52021-09-03T17:52:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.722273722273Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell DeathLingtao Yang0Wei Chen1Li Li2Yueyue Xiao3Shilin Fan4Quan Zhang5Tian Xia6Mengjie Li7Yazhen Hong8Tongjin Zhao9Qiyuan Li10Wen-Hsien Liu11Nengming Xiao12State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaSchool of Medicine, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaSchool of Medicine, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, ChinaFollicular helper T (TFH) cells are specialized CD4+ helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of TFH 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 TFH and Th1 cells, germinal center response, and antibody response to acute viral infection. Ddb1 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 Cul4a and Cul4b in activated CD4+ T cells phenocopied Ddb1-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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.722273/fullDdb1follicular helper T cellshumoral immunityDNA damage responseT cell differentiationG2/M arrest
collection DOAJ
language English
format Article
sources DOAJ
author Lingtao Yang
Wei Chen
Li Li
Yueyue Xiao
Shilin Fan
Quan Zhang
Tian Xia
Mengjie Li
Yazhen Hong
Tongjin Zhao
Qiyuan Li
Wen-Hsien Liu
Nengming Xiao
spellingShingle Lingtao Yang
Wei Chen
Li Li
Yueyue Xiao
Shilin Fan
Quan Zhang
Tian Xia
Mengjie Li
Yazhen Hong
Tongjin Zhao
Qiyuan Li
Wen-Hsien Liu
Nengming Xiao
Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death
Frontiers in Immunology
Ddb1
follicular helper T cells
humoral immunity
DNA damage response
T cell differentiation
G2/M arrest
author_facet Lingtao Yang
Wei Chen
Li Li
Yueyue Xiao
Shilin Fan
Quan Zhang
Tian Xia
Mengjie Li
Yazhen Hong
Tongjin Zhao
Qiyuan Li
Wen-Hsien Liu
Nengming Xiao
author_sort Lingtao Yang
title Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death
title_short Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death
title_full Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death
title_fullStr Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death
title_full_unstemmed Ddb1 Is Essential for the Expansion of CD4+ Helper T Cells by Regulating Cell Cycle Progression and Cell Death
title_sort ddb1 is essential for the expansion of cd4+ helper t cells by regulating cell cycle progression and cell death
publisher Frontiers Media S.A.
series Frontiers in Immunology
issn 1664-3224
publishDate 2021-08-01
description Follicular helper T (TFH) cells are specialized CD4+ helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of TFH 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 TFH and Th1 cells, germinal center response, and antibody response to acute viral infection. Ddb1 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 Cul4a and Cul4b in activated CD4+ T cells phenocopied Ddb1-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.
topic Ddb1
follicular helper T cells
humoral immunity
DNA damage response
T cell differentiation
G2/M arrest
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.722273/full
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