Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4 Trm cells with a Th17 signature and CD8 Trm clusters. In CD, CD4 Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (, and ) along with elevated levels of , and . The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with activation, inducing chemokines (i.e., , , and ) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.

中文翻译：

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克罗恩病患者非炎症肠道组织中 Th17 组织驻留记忆细胞的特征

克罗恩病 (CD) 是一种影响肠壁的慢性炎症性疾病。组织驻留记忆 T (Trm) 细胞与 CD 有关，但其特征仍不清楚。我们的目的是研究 CD 小肠中 Trm 细胞的转录谱和功能特征及其与免疫细胞的相互作用。七名 CD 患者和四名溃疡性结肠炎患者作为对照。单细胞 RNA 测序和配对 T 细胞受体测序评估了小肠组织样本固有层 (LP) 和粘膜下层/固有肌层富集部分 (SM/MP) 中的 T 细胞亚群和转录特征。我们检测到 58,123 个 T 细胞，分为 16 个群体，包括具有 Th17 特征的 CD4 Trm 细胞和 CD8 Trm 簇。在 CD 中，具有 Th17 特征的 CD4 Trm 细胞（称为 Th17 Trm）在 LP 和 SM/MP 区域内的比例显着增加。 Th17 Trm 簇表现出组织驻留标记基因 (、 和 ) 的表达增强，以及 、 和 的水平升高。 CD 中 Th17 Trm 细胞的克隆扩增伴随着跨壁动态电位的增强，如显着较高的迁移分数所示。 CD 突出的 Th17 Trm 细胞表现出增加的干扰素γ (IFNγ) 相关特征，可能与激活、诱导骨髓细胞中的趋化因子（即 、 和 ）有关。我们的研究结果强调了 CD 中整个小肠的 Th17 Trm 细胞升高，通过 IFNγ 诱导和随后骨髓细胞中趋化因子的产生促进疾病发病机制。