The XCL1-XCR1 axis supports intestinal tissue residency and antitumor immunity.

IF 12.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2025-03-03 Epub Date: 2025-01-22 DOI:10.1084/jem.20240776

Amir Ferry, Kianoosh M Mempel, Alexander Monell, Miguel Reina-Campos, Nicole E Scharping, Maximilian Heeg, Kennidy K Takehara, Shiruyeh Schokrpur, Ning Kuo, Robert Saddawi-Konefka, J Silvio Gutkind, Ananda W Goldrath

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引用次数: 0

Abstract

Tissue-resident memory T cells (TRM) provide frontline protection against pathogens and emerging malignancies. Tumor-infiltrating lymphocytes (TIL) with TRM features are associated with improved clinical outcomes. However, the cellular interactions that program TRM differentiation and function are not well understood. Using murine genetic models and targeted spatial transcriptomics, we found that the CD8+ T cell-derived chemokine XCL1 is critical for TRM formation and conventional DC1 (cDC1) supported the positioning of intestinal CD8+ T cells during acute viral infection. In tumors, enforced Xcl1 expression by antigen-specific CD8+ T cells promoted intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. Notably, analysis of human TIL and TRM revealed conserved expression of XCL1 and XCL2. Thus, we have shown that the XCL1-XCR1 axis plays a non-cell autonomous role in guiding intestinal CD8+ TRM spatial differentiation and tumor control.

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XCL1-XCR1轴支持肠道组织驻留和抗肿瘤免疫。

组织驻留记忆T细胞（TRM）提供对病原体和新发恶性肿瘤的一线保护。具有TRM特征的肿瘤浸润淋巴细胞（TIL）与改善的临床结果相关。然而，调控TRM分化和功能的细胞相互作用尚不清楚。利用小鼠遗传模型和靶向空间转录组学，我们发现CD8+ T细胞衍生的趋化因子XCL1对TRM的形成至关重要，而传统的DC1 （cDC1）支持急性病毒感染期间肠道CD8+ T细胞的定位。在肿瘤中，抗原特异性CD8+ T细胞增强Xcl1表达，促进肿瘤内cDC1积累和T细胞持久性，从而提高总生存率。值得注意的是，人类TIL和TRM分析显示XCL1和XCL2保守表达。因此，我们已经证明XCL1-XCR1轴在引导肠道CD8+ TRM空间分化和肿瘤控制中起非细胞自主作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.