Single-cell transcriptomic characterization of microscopic colitis

Abstract 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, t...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59648-8
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Summary:Abstract 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.
ISSN:2041-1723