The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-06-18 DOI:10.1016/j.immuni.2024.05.023
Oliver T. Burton, Orian Bricard, Samar Tareen, Vaclav Gergelits, Simon Andrews, Laura Biggins, Carlos P. Roca, Carly Whyte, Steffie Junius, Aleksandra Brajic, Emanuela Pasciuto, Magda Ali, Pierre Lemaitre, Susan M. Schlenner, Harumichi Ishigame, Brian D. Brown, James Dooley, Adrian Liston
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Abstract

The tissues are the site of many important immunological reactions, yet how the immune system is controlled at these sites remains opaque. Recent studies have identified Foxp3+ regulatory T (Treg) cells in non-lymphoid tissues with unique characteristics compared with lymphoid Treg cells. However, tissue Treg cells have not been considered holistically across tissues. Here, we performed a systematic analysis of the Treg cell population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency, and common molecular dependencies. Tissue Treg cells from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg cell entry and were tissue-agnostic on tissue homing. Together, these results demonstrate that the tissue-resident Treg cell pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Treg cells, characterized by transient multi-tissue migration. This work suggests common regulatory mechanisms may allow pan-tissue Treg cells to safeguard homeostasis across the body.

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组织驻留调节性 T 细胞池是通过瞬时多组织迁移和保守的驻留程序形成的
组织是许多重要免疫反应的发生部位,但免疫系统如何在这些部位受到控制仍不清楚。最近的研究发现,非淋巴组织中的 Foxp3+ 调节性 T(Treg)细胞与淋巴 Treg 细胞相比具有独特的特征。然而,组织 Treg 细胞尚未在不同组织中得到全面考虑。在这里,我们对驻留在全身非淋巴器官中的 Treg 细胞群进行了系统分析,发现了共同的表型、短暂的驻留和共同的分子依赖性。来自不同非淋巴器官的组织Treg细胞共享T细胞受体(TCR)序列,具有驱动多组织Treg细胞进入的功能能力,并且在组织归巢方面与组织无关。这些结果共同证明,除肠道外,大多数非淋巴器官的组织驻留 Treg 细胞池主要由具有广泛自我反应性的 Treg 细胞构成,其特点是瞬时多组织迁移。这项工作表明,共同的调控机制可能使泛组织 Treg 细胞能够保护全身的平衡。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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