Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice.
10.1007/s13238-021-00882-3
- Author:
He LI
1
;
Lei ZHU
1
;
Rong WANG
1
;
Lihui XIE
1
;
Jie REN
2
;
Shuai MA
3
;
Weiqi ZHANG
2
;
Xiuxing LIU
1
;
Zhaohao HUANG
1
;
Binyao CHEN
1
;
Zhaohuai LI
1
;
Huyi FENG
4
;
Guang-Hui LIU
5
;
Si WANG
6
;
Jing QU
7
;
Wenru SU
8
Author Information
1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.
2. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
3. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
4. Chongqing Renji Hospital, University of Chinese Academy of Sciences, Chongqing, 400062, China.
5. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ioz.ac.cn.
6. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. wangsi@xwh.ccmu.edu.cn.
7. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
8. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China. suwenru@gzzoc.com.
- Publication Type:Research Support, Non-U.S. Gov't
- Keywords:
APCs;
Th17 cell;
aging;
experimental autoimmune uveitis;
single-cell sequencing
- MeSH:
Aging;
Animals;
Autoimmune Diseases;
Disease Models, Animal;
Granulocyte-Macrophage Colony-Stimulating Factor/metabolism*;
Mice;
Mice, Inbred C57BL;
Th17 Cells/metabolism*;
Uveitis/pathology*;
Virulence
- From:
Protein & Cell
2022;13(6):422-445
- CountryChina
- Language:English
-
Abstract:
Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
