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<p>Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine and a common cause of chronic diarrhea in older adults. Here, we use single-cell RNA sequencing analysis of colonic mucosal tissue to build a cellular and molecular model for MC. Our results show that in MC, there is a substantial expansion of tissue CD8<sup>+</sup> T cells, likely arising from local expansion following T cell receptor engagement. Within the T cell compartment, MC is characterized by a shift in CD8 tissue-resident memory T cells towards a highly cytotoxic and inflammatory phenotype and expansion of CD4<sup>+</sup> T regulatory cells. These results provide insight into inflammatory cytokines shaping MC pathogenesis and highlight notable similarities and differences with other immune-mediated intestinal diseases, including a common upregulation of <i>IL26</i> and an MC-specific upregulation of <i>IL10</i>. These data help identify targets against enteric T cell subsets as an effective strategy for treatment of MC.</p>

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Single-cell transcriptomic characterization of microscopic colitis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月18日

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  • Stefan Halvorsen,
  • Molly Thomas,
  • Mari Mino-Kenudson,
  • Yuko Kinowaki,
  • Kristin E. Burke,
  • David Morgan,
  • Kaia C. Miller,
  • Katherine M. Williams,
  • Jenny Gurung,
  • Jessica McGoldrick,
  • Megan Hopton,
  • Brooke Hoppe,
  • Nandini Samanta,
  • Sidney Martin,
  • Alice Tirard,
  • Benjamin Y. Arnold,
  • Jessica Tantivit,
  • Joseph Yarze,
  • Kyle Staller,
  • Daniel C. Chung,
  • Alexandra-Chloé Villani,
  • Slim Sassi,
  • Hamed Khalili

摘要

Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine and a common cause of chronic diarrhea in older adults. Here, we use single-cell RNA sequencing analysis of colonic mucosal tissue to build a cellular and molecular model for MC. Our results show that in MC, there is a substantial expansion of tissue CD8+ T cells, likely arising from local expansion following T cell receptor engagement. Within the T cell compartment, MC is characterized by a shift in CD8 tissue-resident memory T cells towards a highly cytotoxic and inflammatory phenotype and expansion of CD4+ T regulatory cells. These results provide insight into inflammatory cytokines shaping MC pathogenesis and highlight notable similarities and differences with other immune-mediated intestinal diseases, including a common upregulation of IL26 and an MC-specific upregulation of IL10. These data help identify targets against enteric T cell subsets as an effective strategy for treatment of MC.