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Single-cell transcriptomic characterization of microscopic colitis

Author

Listed:
  • Stefan Halvorsen

    (Massachusetts General Hospital (MGH))

  • Molly Thomas

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard
    Harvard Medical School (HMS))

  • Mari Mino-Kenudson

    (Harvard Medical School (HMS)
    MGH)

  • Yuko Kinowaki

    (MGH)

  • Kristin E. Burke

    (MGH
    MGH)

  • David Morgan

    (MGH)

  • Kaia C. Miller

    (MGH
    Duke University Health System)

  • Katherine M. Williams

    (MGH)

  • Jenny Gurung

    (MGH)

  • Jessica McGoldrick

    (MGH)

  • Megan Hopton

    (Massachusetts General Hospital (MGH))

  • Brooke Hoppe

    (Massachusetts General Hospital (MGH))

  • Nandini Samanta

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Sidney Martin

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Alice Tirard

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Benjamin Y. Arnold

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Jessica Tantivit

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard)

  • Joseph Yarze

    (MGH)

  • Kyle Staller

    (MGH
    MGH)

  • Daniel C. Chung

    (MGH)

  • Alexandra-Chloé Villani

    (MGH
    Krantz Family Center for Cancer Research, Department of Medicine, MGH
    Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard
    Harvard Medical School (HMS))

  • Slim Sassi

    (Massachusetts General Hospital (MGH)
    Harvard Medical School (HMS)
    MGH)

  • Hamed Khalili

    (Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard
    MGH
    MGH
    Karolinska Institutet)

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.

Suggested Citation

  • 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 & Bro, 2025. "Single-cell transcriptomic characterization of microscopic colitis," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59648-8
    DOI: 10.1038/s41467-025-59648-8
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    References listed on IDEAS

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