Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice
Protein & Cell
; (12): 422-445, 2022.
Article
em En
| WPRIM
| ID: wpr-939868
Biblioteca responsável:
WPRO
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.
Palavras-chave
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Doenças Autoimunes
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Uveíte
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Virulência
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Envelhecimento
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Fator Estimulador de Colônias de Granulócitos e Macrófagos
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Modelos Animais de Doenças
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Células Th17
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Camundongos Endogâmicos C57BL
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Protein & Cell
Ano de publicação:
2022
Tipo de documento:
Article