Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging

Xin Shen; Xianzhi Gao; Yikai Luo; Qianying Xu; Ying Fan; Shenghui Hong; Zhengwei Huang; Xiaoqian Liu; Qianqian Wang; Zuojia Chen; Di Wang; Linrong Lu; Chuan Wu; Han Liang; Lie Wang

doi:10.1038/s43587-023-00453-7

Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging

Xin Shen, Xianzhi Gao, Yikai Luo, Qianying Xu, Ying Fan, Shenghui Hong, Zhengwei Huang, Xiaoqian Liu, Qianqian Wang, Zuojia Chen, Di Wang, Linrong Lu, Chuan Wu, Han Liang, Lie Wang

Bioinformatics & Computational Biology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Aging is accompanied by homeostatic and functional dysregulation of multiple immune cell subsets. Group 3 innate lymphoid cells (ILC3s) constitute a heterogeneous cell population that plays pivotal roles in intestinal immunity. In this study, we found that ILC3s in aged mice exhibited dysregulated homeostasis and function, leading to bacterial and fungal infection susceptibility. Moreover, our data revealed that the enrichment of the H3K4me3 modification in effector genes of aged gut CCR6⁺ ILC3s was specifically decreased compared to young mice counterparts. Disruption of Cxxc finger protein 1 (Cxxc1) activity, a key subunit of H3K4 methyltransferase, in ILC3s led to similar aging-related phenotypes. An integrated analysis revealed Kruppel-like factor 4 (Klf4) as a potential Cxxc1 target. Klf4 overexpression partially restored the differentiation and functional defects seen in both aged and Cxxc1-deficient intestinal CCR6⁺ ILC3s. Therefore, these data suggest that targeting intestinal ILC3s may provide strategies to protect against age-related infections.

Original language	English (US)
Pages (from-to)	965-981
Number of pages	17
Journal	Nature Aging
Volume	3
Issue number	8
DOIs	https://doi.org/10.1038/s43587-023-00453-7
State	Published - Aug 2023

ASJC Scopus subject areas

Neuroscience (miscellaneous)
Aging
Geriatrics and Gerontology

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title = "Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging",

abstract = "Aging is accompanied by homeostatic and functional dysregulation of multiple immune cell subsets. Group 3 innate lymphoid cells (ILC3s) constitute a heterogeneous cell population that plays pivotal roles in intestinal immunity. In this study, we found that ILC3s in aged mice exhibited dysregulated homeostasis and function, leading to bacterial and fungal infection susceptibility. Moreover, our data revealed that the enrichment of the H3K4me3 modification in effector genes of aged gut CCR6+ ILC3s was specifically decreased compared to young mice counterparts. Disruption of Cxxc finger protein 1 (Cxxc1) activity, a key subunit of H3K4 methyltransferase, in ILC3s led to similar aging-related phenotypes. An integrated analysis revealed Kruppel-like factor 4 (Klf4) as a potential Cxxc1 target. Klf4 overexpression partially restored the differentiation and functional defects seen in both aged and Cxxc1-deficient intestinal CCR6+ ILC3s. Therefore, these data suggest that targeting intestinal ILC3s may provide strategies to protect against age-related infections.",

author = "Xin Shen and Xianzhi Gao and Yikai Luo and Qianying Xu and Ying Fan and Shenghui Hong and Zhengwei Huang and Xiaoqian Liu and Qianqian Wang and Zuojia Chen and Di Wang and Linrong Lu and Chuan Wu and Han Liang and Lie Wang",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = aug,

doi = "10.1038/s43587-023-00453-7",

language = "English (US)",

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TY - JOUR

T1 - Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging

AU - Shen, Xin

AU - Gao, Xianzhi

AU - Luo, Yikai

AU - Xu, Qianying

AU - Fan, Ying

AU - Hong, Shenghui

AU - Huang, Zhengwei

AU - Liu, Xiaoqian

AU - Wang, Qianqian

AU - Chen, Zuojia

AU - Wang, Di

AU - Lu, Linrong

AU - Wu, Chuan

AU - Liang, Han

AU - Wang, Lie

PY - 2023/8

Y1 - 2023/8

N2 - Aging is accompanied by homeostatic and functional dysregulation of multiple immune cell subsets. Group 3 innate lymphoid cells (ILC3s) constitute a heterogeneous cell population that plays pivotal roles in intestinal immunity. In this study, we found that ILC3s in aged mice exhibited dysregulated homeostasis and function, leading to bacterial and fungal infection susceptibility. Moreover, our data revealed that the enrichment of the H3K4me3 modification in effector genes of aged gut CCR6+ ILC3s was specifically decreased compared to young mice counterparts. Disruption of Cxxc finger protein 1 (Cxxc1) activity, a key subunit of H3K4 methyltransferase, in ILC3s led to similar aging-related phenotypes. An integrated analysis revealed Kruppel-like factor 4 (Klf4) as a potential Cxxc1 target. Klf4 overexpression partially restored the differentiation and functional defects seen in both aged and Cxxc1-deficient intestinal CCR6+ ILC3s. Therefore, these data suggest that targeting intestinal ILC3s may provide strategies to protect against age-related infections.

AB - Aging is accompanied by homeostatic and functional dysregulation of multiple immune cell subsets. Group 3 innate lymphoid cells (ILC3s) constitute a heterogeneous cell population that plays pivotal roles in intestinal immunity. In this study, we found that ILC3s in aged mice exhibited dysregulated homeostasis and function, leading to bacterial and fungal infection susceptibility. Moreover, our data revealed that the enrichment of the H3K4me3 modification in effector genes of aged gut CCR6+ ILC3s was specifically decreased compared to young mice counterparts. Disruption of Cxxc finger protein 1 (Cxxc1) activity, a key subunit of H3K4 methyltransferase, in ILC3s led to similar aging-related phenotypes. An integrated analysis revealed Kruppel-like factor 4 (Klf4) as a potential Cxxc1 target. Klf4 overexpression partially restored the differentiation and functional defects seen in both aged and Cxxc1-deficient intestinal CCR6+ ILC3s. Therefore, these data suggest that targeting intestinal ILC3s may provide strategies to protect against age-related infections.

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Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging

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