Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking....Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.展开更多
基金This work was supported by the National Key Research and Development Program of China(2017YFA0105804)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010000)+8 种基金the National Key Research and Development Program of China(2018YFC2000100,2017YFA0103304,2017YFA0102802,2018YFA0107203)the National Natural Science Foundation of China(81670897,81625009,91749202.81861168034,81921006,31671429,91949209,91749123,81671377,81822018,81870228,81922027,81701388,81601233)the Program of the Beijing Municipal Science and Technology Commission(Z191100001519005)Bejing Natural Science Foun-dation(Z190019)Bejing Municipal Commission of Health and Family Planning(PXM2018026283_000002)Advanced Innovation Center for Human Brain Protection(3500-1192012)the Key Research Program of the Chinese Academy of Sciences(KFZD-SW-221)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08),Youth Innovation Promotion Association of CAS(2016093)the State Key Laboratory of Membrane Biology and the State Key Laboratory of Stem Cell and Reproductive Biology.
文摘Age-associated changes in immune cells have been linked to an increased risk for infection.However,a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking.Here,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19.We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic cells.In addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with age.Notably,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senes-cence.Therefore,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
