Single-cell transcriptomic characterization of microscopic colitis

• Published in: Nature communications Vol. 16; no. 1; pp. 4618 - 16
• Main Authors: Halvorsen, Stefan, Thomas, Molly, Mino-Kenudson, Mari, Kinowaki, Yuko, Burke, Kristin E., Morgan, David, Miller, Kaia C., Williams, Katherine M., Gurung, Jenny, McGoldrick, Jessica, Hopton, Megan, Hoppe, Brooke, Samanta, Nandini, Martin, Sidney, Tirard, Alice, Arnold, Benjamin Y., Tantivit, Jessica, Yarze, Joseph, Staller, Kyle, Chung, Daniel C., Villani, Alexandra-Chloé, Sassi, Slim, Khalili, Hamed
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 14/32; 14/63; 38/91; 631/250/1619; 631/250/347; 631/337/2019; 692/420/256/2515; 692/699/1503; Animals; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Colitis; Colitis, Microscopic - genetics; Colitis, Microscopic - immunology; Colitis, Microscopic - metabolism; Colitis, Microscopic - pathology; Colon - immunology; Colon - metabolism; Colon - pathology; Cytotoxicity; Diarrhea; Female; Gene Expression Profiling; Gene sequencing; Humanities and Social Sciences; Humans; Immune system; Immunological memory; Immunoregulation; Inflammatory bowel disease; Inflammatory diseases; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-10 - metabolism; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Large intestine; Localization; Lymphocytes; Lymphocytes T; Male; Memory cells; Mice; Mice, Inbred C57BL; multidisciplinary; Older people; Pathogenesis; Phenotypes; Science; Science (multidisciplinary); Sequence analysis; Single-Cell Analysis - methods; T cell receptors; T-Lymphocytes, Regulatory - immunology; Transcriptome; Transcriptomics; Up-regulation
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-025-59648-8

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. Microscopic colitis is a chronic inflammatory disease of the large intestine. Here the authors use single-cell RNA transcriptomic profiling and tissue localization studies to characterise the colon immune cell populations in MC, showing expansion of CD8 T cells with diverse TCR clonotypes and expression of CD4 T reg cell signatures.