英国伦敦国王学院免疫生物学系Adrian C. Hayday和Robin J. Dart共同合作，近期取得重要工作进展。他们研究发现BTNL蛋白对保守γδ T细胞的选择性限制了人类炎症性肠病的进展。相关研究成果2023年9月15日在线发表于《科学》杂志上。

据介绍，鼠上皮内γδ T细胞包括由上皮嗜丁蛋白样（BTNL）异聚体选择的不同组织保护细胞。

为了确定这种生物学特性在人类中是否保守，研究人员对结肠γδ T细胞区室进行了表征，确定了一个多样化的库，其中包括共表达T细胞受体Vγ4和上皮结合整合素CD103的表型不同的亚群。该亚群在炎症性肠病中不成比例地减少和失调，而治疗中CD103⁺γδT细胞的恢复与炎症性肠病的持续缓解相关。

此外，生殖腺BTNL3/BTNL8亚型的人也表现出CD103⁺Vγ4⁺细胞的失调和缺失，将其确定为渗透性克罗恩病（CD）的危险因素。

因此，BTNL依赖性选择以及不同组织固有γδT细胞的维持似乎是演化上保守的轴，限制了全球发病率不断增加的复杂、多因素、组织损伤性疾病的进展。

附：英文全文

Title: Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease

Author: Robin J. Dart, Iva Zlatareva, Pierre Vantourout, Efstathios Theodoridis, Ariella Amar, Shichina Kannambath, Philip East, Timothy Recaldin, John C. Mansfield, Christopher A. Lamb, Miles Parkes, Peter M. Irving, Natalie J. Prescott, Adrian C. Hayday

Issue&Volume: 2023-09-15

Abstract: Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103+γδ T cell restoration was associated with sustained inflammatory bowel disease remission. Moreover, CD103+Vγ4+cell dysregulation and loss were also displayed by humans with germline BTNL3/BTNL8 hypomorphism, which we identified as a risk factor for penetrating Crohn’s disease (CD). Thus, BTNL-dependent selection and/or maintenance of distinct tissue-intrinsic γδ T cells appears to be an evolutionarily conserved axis limiting the progression of a complex, multifactorial, tissue-damaging disease of increasing global incidence.

DOI: adh0301

Source: https://www.science.org/doi/10.1126/science.adh0301