文章基本信息

标题：Circulation of gut-preactivated naïve CD8 T cells enhances antitumor immunity in B cell-defective mice
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作者：Maryam Akrami ; Rosemary Menzies ; Kenji Chamoto 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：38
页码：23674-23683
DOI：10.1073/pnas.2010981117
出版社：The National Academy of Sciences of the United States of America
摘要：The gut microbiome has garnered attention as an effective target to boost immunity and improve cancer immunotherapy. We found that B cell-defective (BCD) mice, such as µ-membrane targeted deletion (µMT) and activation-induced cytidine deaminase (AID) knockouts (KOs), have elevated antitumor immunity under specific pathogen-free but not germ-free conditions. Microbial dysbiosis in these BCD mice enriched the type I IFN (IFN) signature in mucosal CD8 T cells, resulting in up-regulation of the type I IFN-inducible protein stem cell antigen-1 (Sca-1). Among CD8 T cells, naïve cells predominantly circulate from the gut to the periphery, and those that had migrated from the mesenteric lymph nodes (mLNs) to the periphery had significantly higher expression of Sca-1. The gut-educated Sca-1 naïve subset is endowed with enhanced mitochondrial activity and antitumor effector potential. The heterogeneity and functional versatility of the systemic naïve CD8 T cell compartment was revealed by single-cell analysis and functional assays of CD8 T cell subpopulations. These results indicate one of the potential mechanisms through which microbial dysbiosis regulates antitumor immunity.
关键词：IgA ; type I IFN signaling ; circulation between gut and periphery ; gut-microbiota education ; mitochondrial activation