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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59648-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Stefan Halvorsen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-fb92c66d3b014006b2bc27eb7a853040 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-fb92c66d3b014006b2bc27eb7a8530402025-08-20T03:48:02ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59648-8Single-cell transcriptomic characterization of microscopic colitisStefan Halvorsen0Molly Thomas1Mari Mino-Kenudson2Yuko Kinowaki3Kristin E. Burke4David Morgan5Kaia C. Miller6Katherine M. Williams7Jenny Gurung8Jessica McGoldrick9Megan Hopton10Brooke Hoppe11Nandini Samanta12Sidney Martin13Alice Tirard14Benjamin Y. Arnold15Jessica Tantivit16Joseph Yarze17Kyle Staller18Daniel C. Chung19Alexandra-Chloé Villani20Slim Sassi21Hamed Khalili22Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH)Center for Immunology and Inflammatory Diseases, Department of Medicine, MGHHarvard Medical School (HMS)Department of Pathology, HMS, MGHDivision of Gastroenterology, Department of Medicine, MGHClinical and Translational Epidemiology Unit, MGHClinical and Translational Epidemiology Unit, MGHClinical and Translational Epidemiology Unit, MGHClinical and Translational Epidemiology Unit, MGHClinical and Translational Epidemiology Unit, MGHCenter for Computational and Integrative Biology, Massachusetts General Hospital (MGH)Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH)Center for Immunology and Inflammatory Diseases, Department of Medicine, MGHCenter for Immunology and Inflammatory Diseases, Department of Medicine, MGHCenter for Immunology and Inflammatory Diseases, Department of Medicine, MGHCenter for Immunology and Inflammatory Diseases, Department of Medicine, MGHCenter for Immunology and Inflammatory Diseases, Department of Medicine, MGHDivision of Gastroenterology, Department of Medicine, MGHDivision of Gastroenterology, Department of Medicine, MGHDivision of Gastroenterology, Department of Medicine, MGHCenter for Immunology and Inflammatory Diseases, Department of Medicine, MGHCenter for Computational and Integrative Biology, Massachusetts General Hospital (MGH)Broad Institute of Massachusetts Institute of Technology (MIT) and HarvardAbstract 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.https://doi.org/10.1038/s41467-025-59648-8 |
| spellingShingle | 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 Single-cell transcriptomic characterization of microscopic colitis Nature Communications |
| title | Single-cell transcriptomic characterization of microscopic colitis |
| title_full | Single-cell transcriptomic characterization of microscopic colitis |
| title_fullStr | Single-cell transcriptomic characterization of microscopic colitis |
| title_full_unstemmed | Single-cell transcriptomic characterization of microscopic colitis |
| title_short | Single-cell transcriptomic characterization of microscopic colitis |
| title_sort | single cell transcriptomic characterization of microscopic colitis |
| url | https://doi.org/10.1038/s41467-025-59648-8 |
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