Single-cell transcriptomic characterization of microscopic colitis
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 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.
Authors
- Hamed Khalili (ORCID: https://orcid.org/0000-0002-7956-6941)
- Jessica McGoldrick
- Benjamin Y. Arnold
- Stefan Halvorsen (ORCID: https://orcid.org/0000-0001-8150-6780)
- Molly Thomas (ORCID: https://orcid.org/0000-0002-1393-6559)
- Sidney Martin
- Megan Hopton (ORCID: https://orcid.org/0009-0006-4761-9849)
- Alexandra–Chloé Villani (ORCID: https://orcid.org/0000-0001-7461-0408)
- Jessica Tantivit (ORCID: https://orcid.org/0000-0002-2179-0377)
- Yuko Kinowaki (ORCID: https://orcid.org/0000-0001-8907-2569)
- Kaia C. Miller (ORCID: https://orcid.org/0000-0002-3647-7287)
- David M. L. Morgan (ORCID: https://orcid.org/0000-0001-9994-2847)
- Nandini Samanta
- Brooke Hoppe (ORCID: https://orcid.org/0000-0001-5562-1312)
- Joseph C. Yarze (ORCID: https://orcid.org/0000-0003-0192-6385)
- Alice Tirard
- Mari A. Mino-Kenudson (ORCID: https://orcid.org/0000-0002-9092-2265)
- Kyle Staller (ORCID: https://orcid.org/0000-0003-4925-4290)
- Kristin E. Burke (ORCID: https://orcid.org/0000-0002-2536-5538)
- Daniel C. Chung (ORCID: https://orcid.org/0000-0001-8226-7005)
- Slim Sassi (ORCID: https://orcid.org/0000-0001-6329-4980)
- Jenny Gurung
- Katherine M. Williams
Institutions
- Broad Institute (US)
- nLIGHT (United States) (US)
- Harvard University (US)
- MGH Institute of Health Professions (US)
- Karolinska Institutet (SE)
- Massachusetts General Hospital (US)
- Duke University Health System (US)
- Center for Cancer Research (US)
- Massachusetts Institute of Technology (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-18
- DOI
- https://doi.org/10.1038/s41467-025-59648-8
- Citations
- 2
- Primary Topic
- Microscopic Colitis
- Type
- article
- Field-Weighted Citation Impact
- 2.71
Funders
- American College of Gastroenterology
- Karolinska Institutet
- National Institutes of Health