Elevated CD153 Expression on Aged T Follicular Helper Cells is Vital for B cell Responses.
Elevated CD153 Expression on Aged T Follicular Helper Cells is Vital for B cell Responses.
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衰老 T 滤泡辅助细胞上 CD153 表达升高对于 B 细胞反应至关重要。
DOI：
10.1101/2023.03.17.533214
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Hildeman,DavidA
中科院分区：
文献类型：
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作者：
Thomas,AlyssaL;Wayman,JosephA;Almanan,Maha;Bejjani,AnthonyT;Miraldi,EmilyR;Chougnet,ClaireA;Hildeman,DavidA
我们最近的数据显示，产生IL-10的T滤泡辅助人群(Tfh10)的异常数量随着年龄的增长而急剧积累，并与年龄相关的疫苗反应性下降有关。通过对青年和老年小鼠IL-10+和IL-10CD4+记忆−+T细胞的单细胞基因表达和染色质可及性分析，我们证实了CD153在老年Tfh和Tfh10细胞上的表达增加。在机制上，我们通过c-Maf将炎症(IL-6水平增加)与TFH细胞CD153表达增加联系起来。令人惊讶的是，在老年小鼠中阻断CD153显著降低了疫苗驱动的抗体反应，这与抗原特异性Tfh细胞上ICOS表达的减少有关。综上所述，这些数据表明IL-6/c-Maf/CD153通路对于维持ICOS的表达至关重要。因此，尽管在疫苗和衰老的背景下，总的Tfh介导的B细胞反应减少，但我们的数据表明，Tfh细胞上CD153的高表达增强了老年小鼠剩余的Tfh功能。
Our recent data showed that an aberrant IL-10-producing T follicular helper population (Tfh10) accumulates dramatically with age and is associated with age-related declines in vaccine responsiveness. Through single cell gene expression and chromatin accessibility analysis of IL-10+ and IL-10− memory CD4+ T cells from young and aged mice, we identified increased expression of CD153 on aged Tfh and Tfh10 cells. Mechanistically, we linked inflammaging (increased IL-6 levels) to elevated CD153 expression of Tfh cells through c-Maf. Surprisingly, blockade of CD153 in aged mice significantly reduced their vaccine-driven antibody response, which was associated with decreased expression of ICOS on antigen-specific Tfh cells. Combined, these data show that an IL-6/c-Maf/CD153 circuit is critical for maintaining ICOS expression. Thus, although overall Tfh-mediated B cell responses are reduced in the context of vaccines and aging, our data suggest that elevated expression of CD153 on Tfh cells potentiates the remaining Tfh function in aged mice.