이윤호 (울산대학교 의과대학, 서울아산병원) | 한빛사논문 > 한빛사

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조회476

울산대학교 의과대학, 서울아산병원

J. Autoimmun., Volume 145, May 2024, 103206 | https://doi.org/10.1016/j.jaut.2024.103206 Characterization of Th17 tissue-resident memory cells in non-inflamed intestinal tissue of Crohn's disease patients

Yoonho Lee ^a, Jiwon Baek ^a, Sojung Park ^a, Yongjae Kim^a, Sung Wook Hwang ^b, Jong Lyul Lee^c, Sang Hyoung Park ^b, Jihun Kim ^d, Suk-Kyun Yang ^b, Buhm Han ^e, Mi-Na Kweon ^f, Kyuyoung Song ^a, Yong Sik Yoon^c, Byong Duk Ye ^b, Ho-Su Lee ^a

^aDepartment of Biochemistry and Molecular Biology, Asan Medical Center, Brain Korea 21 Project, University of Ulsan College of Medicine, Seoul, South Korea

^bDepartment of Gastroenterology, Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^cDivision of Colon and Rectal Surgery, Department of Surgery, Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^dDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^eDepartment of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, South Korea

^fMucosal Immunology Laboratory, Asan Medical Center, Brain Korea 21 Project, University of Ulsan College of Medicine, Seoul, South Korea

Corresponding authors: Yong Sik Yoon, Byong Duk Ye, Ho-Su Lee

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 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 (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 possibly 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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-04-01)
연구진국내 연구진
분야 의약학 > 응용의학

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