Acute graft-versus-host disease (GVHD) represents a severe, T cell–driven inflammatory complication following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD often affects the intestine and is associated with a poor prognosis. Although frequently detectable, proinflammatory mechanisms exerted by intestinal tissue–infiltrating Th cell subsets remain to be fully elucidated. Here, we show that the Th17-defining transcription factor basic leucine zipper transcription factor ATF-like (BATF) was strongly regulated across human and mouse intestinal GVHD tissues. Studies in complete MHC-mismatched and minor histocompatibility–mismatched (miHA-mismatched) GVHD models revealed that BATF-expressing T cells were functionally indispensable for intestinal GVHD manifestation. Mechanistically, BATF controlled the formation of colon-infiltrating, IL-7 receptor–positive (IL-7R⁺), granulocyte-macrophage colony-stimulating factor–positive (GM-CSF⁺), donor T effector memory (Tem) cells. This T cell subset was sufficient to promote intestinal GVHD, while its occurrence was largely dependent on T cell–intrinsic BATF expression, required IL-7–IL-7R interaction, and was enhanced by GM-CSF. Thus, this study identifies BATF-dependent pathogenic GM-CSF⁺ effector T cells as critical promoters of intestinal inflammation in GVHD and hence putatively provides mechanistic insight into inflammatory processes previously assumed to be selectively Th17 driven.

中文翻译：

---

依赖BATF的IL-7R ^hi GM-CSF ⁺ T细胞控制肠道移植物抗宿主病

异体造血细胞移植（allo-HCT）后，急性移植物抗宿主病（GVHD）代表了严重的T细胞驱动性炎性并发症。GVHD通常会影响肠道，并伴有不良的预后。尽管可以经常检测到，但肠组织浸润性Th细胞亚群发挥的促炎机制仍有待充分阐明。在这里，我们显示Th17定义转录因子碱性亮氨酸拉链转录因子ATF样（BATF）在人类和小鼠肠道GVHD组织中受到强烈调节。对完整的MHC不匹配和轻微组织相容性不匹配（miHA不匹配）的GVHD模型进行的研究表明，表达BATF的T细胞在功能上对于肠道GVHD表现是必不可少的。从机理上讲，BATF控制着结肠浸润的形成，⁺），粒细胞巨噬细胞集落刺激因子阳性（GM-CSF ⁺），供体T效应记忆（Tem）细胞。这种T细胞亚群足以促进肠道GVHD，而它的发生在很大程度上取决于T细胞内在的BATF表达，需要IL-7-IL-7R相互作用，并被GM-CSF增强。因此，这项研究确定了依赖BATF的致病性GM-CSF ⁺效应T细胞作为GVHD肠道炎症的关键启动子，因此推论提供了对以前被认为是由Th17选择性驱动的炎症过程的机械观察。