크론병에서 조직 상주 기억 T 세포의 단일 세포 전사체 분석

Abstract

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 identified 58,123 T cells grouped into 16 populations, including the Th17 Trm, CD4+ Trm, and CD8+ Trm clusters. In patients with CD, we identified Trm cells with a Th17 signature (termed Th17 Trm) in the bowel, demonstrating significantly increased proportions of the Th17 Trm cluster in both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of canonical tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. 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 linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) 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.