Department of Microbiology and Immunology, Center for Infectious Diseases, Renaissance School of Medicine, Stony Brook University , Stony Brook, NY, USA.
Lung Biology Center, Department of Medicine, University of California, San Francisco , San Francisco, CA, USA.
J Exp Med. 2023 May 1;220(5). doi: 10.1084/jem.20210923. Epub 2023 Feb 21.
CD8 tissue-resident memory T (TRM) cells provide frontline protection at barrier tissues; however, mechanisms regulating TRM cell development are not completely understood. Priming dictates the migration of effector T cells to the tissue, while factors in the tissue induce in situ TRM cell differentiation. Whether priming also regulates in situ TRM cell differentiation uncoupled from migration is unclear. Here, we demonstrate that T cell priming in the mesenteric lymph nodes (MLN) regulates CD103+ TRM cell differentiation in the intestine. In contrast, T cells primed in the spleen were impaired in the ability to differentiate into CD103+ TRM cells after entry into the intestine. MLN priming initiated a CD103+ TRM cell gene signature and licensed rapid CD103+ TRM cell differentiation in response to factors in the intestine. Licensing was regulated by retinoic acid signaling and primarily driven by factors other than CCR9 expression and CCR9-mediated gut homing. Thus, the MLN is specialized to promote intestinal CD103+ CD8 TRM cell development by licensing in situ differentiation.
CD8 组织驻留记忆 T（TRM）细胞为屏障组织提供一线保护；然而，调节 TRM 细胞发育的机制尚不完全清楚。启动决定效应 T 细胞向组织的迁移，而组织中的因素诱导原位 TRM 细胞分化。启动是否也调节与迁移分离的原位 TRM 细胞分化尚不清楚。在这里，我们证明了肠系膜淋巴结（MLN）中的 T 细胞启动调节了肠道中的 CD103+ TRM 细胞分化。相比之下，进入肠道后，在脾脏中被激活的 T 细胞分化为 CD103+ TRM 细胞的能力受损。MLN 启动引发了 CD103+ TRM 细胞基因特征，并授权快速响应肠道因子的 CD103+ TRM 细胞分化。许可由视黄酸信号调节，主要由 CCR9 表达和 CCR9 介导的肠道归巢以外的因素驱动。因此，MLN 专门通过许可原位分化来促进肠道 CD103+ CD8 TRM 细胞的发育。
