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울산대학교 의과대학, 서울아산병원

Exp. Mol. Med., Jul 06 2026, | https://doi.org/10.1038/s12276-026-01763-7 Granzyme K CD8⁺ T cells with tissue-resident features promote intestinal inflammation in patients with Crohn's disease

Yoonho Lee¹, Tae-Young Kim², Yongjae Kim¹, Jiwon Baek¹, Hwan Park¹, Do Kyung Yoon¹, Sung Wook Hwang³, Jong Lyul Lee⁴, Sang Hyoung Park³, Jihun Kim⁵, Suk-Kyun Yang³, Buhm Han⁶, Mi-Na Kweon², Kyuyoung Song¹, Yong Sik Yoon^4*, Byong Duk Ye^3* and Ho-Su Lee^1*

¹Department of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
²Mucosal Immunology Laboratory, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
³Department of Gastroenterology, Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁴Division of Colon and Rectal Surgery, Department of Surgery, Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁵Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁶Department of Biomedical Sciences, BK21 Plus Biomedical Science Project, Seoul National University College of Medicine, Seoul, Korea.

^*Corresponding authors
Correspondence to Yong Sik Yoon, Byong Duk Ye or Ho-Su Lee.

Abstract

The role of CD8⁺ T cells in Crohn's disease (CD) pathogenesis remains incompletely understood. This study aimed to characterize CD8⁺ T cells in CD and elucidate their potential contribution to intestinal inflammation. T cells from blood and intestinal tissues of 15 patients with CD were analyzed using single-cell RNA and T cell receptor sequencing. Spatial transcriptomics was conducted on inflamed intestinal tissues from two patients. Analysis of 41,699 CD8⁺ T cells identified distinct subsets characterized by differential granzyme expression: granzyme B (GZMB⁺) CD8⁺ T cells, predominantly in blood with high cytotoxic potential, and granzyme K (GZMK⁺) CD8⁺ T cells, enriched in intestinal tissue with lower cytotoxic potential. In the small intestine, GZMK⁺CD8⁺ T cells displayed enhanced tissue residency signatures (for example, CXCR6) and downregulated egress-related genes (S1PR1and S1PR5). GZMK⁺CD8⁺ T cells displayed robust interactions with myeloid cells via the CXCR3-CXCL9/10 axis, coupled with notable colocalization in the small intestine. Pharmacological inhibition of GZMK alleviated intestinal inflammation and tissue damage in a murine model of intestinal injury, supporting its role in modulating inflammatory responses. Together, these findings highlight GZMK as a potential modulator of intestinal inflammation and a candidate for further therapeutic investigation.

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