RESEARCH ARTICLE

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

  • He Li 1 ,
  • Lei Zhu 1 ,
  • Rong Wang 1 ,
  • Lihui Xie 1 ,
  • Jie Ren 5,6,8 ,
  • Shuai Ma 2,6,9,10 ,
  • Weiqi Zhang 5,6,7,8 ,
  • Xiuxing Liu 1 ,
  • Zhaohao Huang 1 ,
  • Binyao Chen 1 ,
  • Zhaohuai Li 1 ,
  • Huyi Feng 10 ,
  • Guang-Hui Liu , 2,4,6,9 ,
  • Si Wang , 4,7 ,
  • Jing Qu , 3,6,9 ,
  • Wenru Su , 1
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  • 1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China
  • 2. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 3. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 4. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China
  • 5. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
  • 6. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
  • 7. Aging Translational Medicine Center, International Center for Aging and Cancer, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • 8. China National Center for Bioinformation, Beijing 100101, China
  • 9. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
  • 10. Chongqing Renji Hospital, University of Chinese Academy of Sciences, Chongqing 400062, China

Received date: 02 Aug 2021

Accepted date: 13 Sep 2021

Published date: 15 Jun 2022

Copyright

2021 The Author(s)

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.

Cite this article

He Li , Lei Zhu , Rong Wang , Lihui Xie , Jie Ren , Shuai Ma , Weiqi Zhang , Xiuxing Liu , Zhaohao Huang , Binyao Chen , Zhaohuai Li , Huyi Feng , Guang-Hui Liu , Si Wang , Jing Qu , Wenru Su . Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice[J]. Protein & Cell, 0 , 13(6) : 422 -445 . DOI: 10.1007/s13238-021-00882-3

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