Scholarlink

<p>The role of CD8<sup>+</sup> T cells in Crohn’s disease (CD) pathogenesis remains incompletely understood. This study aimed to characterize CD8<sup>+</sup> 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<sup>+</sup> T cells identified distinct subsets characterized by differential granzyme expression: granzyme B (GZMB<sup>+</sup>) CD8<sup>+</sup> T cells, predominantly in blood with high cytotoxic potential, and granzyme K (GZMK<sup>+</sup>) CD8<sup>+</sup> T cells, enriched in intestinal tissue with lower cytotoxic potential. In the small intestine, GZMK<sup>+</sup>CD8<sup>+</sup> T cells displayed enhanced tissue residency signatures (for example, <i>CXCR6</i>) and downregulated egress-related genes (<i>S1PR1</i>and <i>S1PR5</i>). GZMK<sup>+</sup>CD8<sup>+</sup> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Granzyme K CD8⁺ T cells with tissue-resident features promote intestinal inflammation in patients with Crohn’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月6日

查看全文
  • Yoonho Lee,
  • Tae-Young Kim,
  • Yongjae Kim,
  • Jiwon Baek,
  • Hwan Park,
  • Do Kyung Yoon,
  • Sung Wook Hwang,
  • Jong Lyul Lee,
  • Sang Hyoung Park,
  • Jihun Kim,
  • Suk-Kyun Yang,
  • Buhm Han,
  • Mi-Na Kweon,
  • Kyuyoung Song,
  • Yong Sik Yoon,
  • Byong Duk Ye,
  • Ho-Su Lee

摘要

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.