CD8+T细胞在肠道和骨髓之间的迁移回路影响抗肿瘤免疫力

IF 17.3 1区 生物学 Q1 CELL BIOLOGY
Rong-Yi Shi, Neng Zhou, Li Xuan, Zhong-Hui Jiang, Jing Xia, Jian-Min Zhu, Kai-Ming Chen, Guo-Li Zhou, Guo-Pan Yu, Jun Zhang, Chuanxin Huang, Ai-Bin Liang, Kai-Wei Liang, Hao Zhang, Jian-Feng Chen, Dachuan Zhang, Yi Zhong, Qi-Fa Liu, Guo-Qiang Chen, Cai-Wen Duan
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引用次数: 0

摘要

免疫疗法会在外周循环 T 细胞中引发全身性抗肿瘤免疫反应。然而,器官间的 T 细胞运输回路及其对抗肿瘤免疫的贡献在很大程度上仍不为人所知。在这里,我们在多种小鼠白血病模型中发现,骨髓(BM)中白血病细胞的大量浸润刺激 CD8+CD44+CD62L+ 中枢记忆 T 细胞转变为 CD8+CD44-CD62L- T 细胞,即器官间迁移 T 细胞(TIM 细胞)。在白血病发生过程中,TIM 细胞通过上调整合素 β7 和下调 C-X-C motif 趋化因子受体 3 从 BM 转移到肠道。在接受免疫性化疗时,这些来源于 BM 的 TIM 细胞会通过整合素 α4 与血管细胞粘附分子 1 的相互作用从肠道返回 BM。阻断 C-X-C motif 趋化因子受体 3 的功能可通过加强 T 细胞的迁移来增强对白血病的免疫反应。在白血病患者身上也能观察到这种现象。总之,我们发现了一种未被发现的 T 细胞肠-BM 转运回路,它有助于免疫化疗的抗肿瘤效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity

Trafficking circuit of CD8+ T cells between the intestine and bone marrow governs antitumour immunity
Immunotherapy elicits a systemic antitumour immune response in peripheral circulating T cells. However, the T cell trafficking circuit between organs and their contributions to antitumour immunity remain largely unknown. Here we show in multiple mouse leukaemia models that high infiltration of leukaemic cells in bone marrow (BM) stimulates the transition of CD8+CD44+CD62L+ central memory T cells into CD8+CD44–CD62L– T cells, designated as inter-organ migratory T cells (TIM cells). TIM cells move from the BM to the intestine by upregulating integrin β7 and downregulating C-X-C motif chemokine receptor 3 during leukaemogenesis. Upon immunogenic chemotherapy, these BM-derived TIM cells return from the intestine to the BM through integrin α4–vascular cell adhesion molecule 1 interaction. Blocking C-X-C motif chemokine receptor 3 function boosts the immune response against leukaemia by enhancing T cell trafficking. This phenomenon can also be observed in patients with leukaemia. In summary, we identify an unrecognized intestine–BM trafficking circuit of T cells that contributes to the antitumour effects of immunogenic chemotherapy. Shi, Zhou, Xuan, Jiang et al. identify a population of CD8+ T cells that migrate from bone marrow to the small intestine during leukaemogenesis and then traffic back to contribute to anti-leukaemia immune responses during chemotherapy treatment.
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来源期刊
Nature Cell Biology
Nature Cell Biology 生物-细胞生物学
CiteScore
28.40
自引率
0.90%
发文量
219
审稿时长
3 months
期刊介绍: Nature Cell Biology, a prestigious journal, upholds a commitment to publishing papers of the highest quality across all areas of cell biology, with a particular focus on elucidating mechanisms underlying fundamental cell biological processes. The journal's broad scope encompasses various areas of interest, including but not limited to: -Autophagy -Cancer biology -Cell adhesion and migration -Cell cycle and growth -Cell death -Chromatin and epigenetics -Cytoskeletal dynamics -Developmental biology -DNA replication and repair -Mechanisms of human disease -Mechanobiology -Membrane traffic and dynamics -Metabolism -Nuclear organization and dynamics -Organelle biology -Proteolysis and quality control -RNA biology -Signal transduction -Stem cell biology
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