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.

衰老引起的免疫系统变化与感染和疫苗接种失败的发生率较高有关。淋巴结可以过滤淋巴液以识别和抵抗感染，在此过程中发挥着核心作用。然而，目前还缺乏对衰老对淋巴结和相关自身免疫性疾病影响的仔细表征。我们将单细胞 RNA 测序 (scRNA-seq) 与流式细胞术相结合，描绘了患有或不患有实验性自身免疫性葡萄膜炎 (EAU) 的年轻和年老小鼠的颈部引流淋巴结 (CDLN) 的免疫细胞图谱。我们发现衰老过程中 CDLN 的细胞成分发生了广泛而复杂的变化。当面临自身免疫挑战时，与年轻小鼠相比，年老小鼠出现更轻微的 EAU。在这个 EAU 过程中，我们强调 T 辅助细胞 17 细胞 (Th17) 的致病性受到抑制，如老年小鼠 GM-CSF 分泌减少所示。 GM-CSF 分泌减少有助于减轻抗原呈递细胞 (APC) 分泌 IL-23，进而可能削弱 APC 促进 Th17 细胞致病性的作用。同时，我们的研究进一步揭示了衰老通过降低来自 CDLN 的 Th17 细胞中 IL-23R 的转录本和蛋白水平来下调 GM-CSF 的分泌。总体而言，衰老改变了免疫细胞反应，特别是通过减弱 Th17 细胞，抵消了老年小鼠的 EAU 挑战。