作者
Saad Khan, Mainak Chakraborty, Fei Wu, Nan Chen, Tao Wang, Yi Tao Chan, Azin Sayad, Juan Diego Sánchez Vásquez, Max Kotlyar, Khiem Nguyen, Yingxiang Huang, Faisal J Alibhai, Minna Woo, Ren-Ke Li, Mansoor Husain, Igor Jurisica, Adam J Gehring, Pamela S Ohashi, David Furman, Sue Tsai, Shawn Winer, Daniel A Winer
发表日期
2023/9/14
期刊
bioRxiv
出版商
Cold Spring Harbor Laboratory Preprints
简介
A dysregulated adaptive immune system is a key feature of aging, and is associated with age-related chronic diseases and mortality. Most notably, aging is linked to a loss in the diversity of the T cell repertoire and expansion of activated inflammatory age-related T cell subsets, though the main drivers of these processes are largely unknown. Here, we find that T cell aging is directly influenced by B cells. Using multiple models of B cell manipulation and single-cell omics, we find B cells to be a major cell type that is largely responsible for the age-related reduction of naive T cells, their associated differentiation towards pathogenic immunosenescent T cell subsets, and for the clonal restriction of their T cell receptor (TCR). Accordingly, we find that these pathogenic shifts can be therapeutically targeted via CD20 monoclonal antibody treatment. Mechanistically, we uncover a new role for insulin receptor signaling in …
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