Single-cell transcriptomic characterization of microscopic colitis
- 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
2025-05-18
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.