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...
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| Published in | Nature communications Vol. 16; no. 1; pp. 4618 - 16 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
18.05.2025
Nature Publishing Group Nature Portfolio |
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| 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.
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. |
|---|---|
| AbstractList | 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. 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. 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. 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 (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. 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 (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. |
| ArticleNumber | 4618 |
| Author | Morgan, David Gurung, Jenny Sassi, Slim Hopton, Megan Chung, Daniel C. Villani, Alexandra-Chloé Arnold, Benjamin Y. Khalili, Hamed Kinowaki, Yuko Burke, Kristin E. McGoldrick, Jessica Samanta, Nandini Martin, Sidney Thomas, Molly Miller, Kaia C. Halvorsen, Stefan Hoppe, Brooke Mino-Kenudson, Mari Tantivit, Jessica Staller, Kyle Williams, Katherine M. Tirard, Alice Yarze, Joseph |
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Kristin E. organization: Division of Gastroenterology, Department of Medicine, MGH, Clinical and Translational Epidemiology Unit, MGH – sequence: 6 givenname: David surname: Morgan fullname: Morgan, David organization: Clinical and Translational Epidemiology Unit, MGH – sequence: 7 givenname: Kaia C. orcidid: 0000-0002-3647-7287 surname: Miller fullname: Miller, Kaia C. organization: Clinical and Translational Epidemiology Unit, MGH, Department of Medicine, Duke University Health System – sequence: 8 givenname: Katherine M. surname: Williams fullname: Williams, Katherine M. organization: Clinical and Translational Epidemiology Unit, MGH – sequence: 9 givenname: Jenny surname: Gurung fullname: Gurung, Jenny organization: Clinical and Translational Epidemiology Unit, MGH – sequence: 10 givenname: Jessica surname: McGoldrick fullname: McGoldrick, Jessica organization: Clinical and Translational Epidemiology Unit, MGH – sequence: 11 givenname: Megan surname: Hopton fullname: Hopton, Megan organization: Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH) – sequence: 12 givenname: Brooke surname: Hoppe fullname: Hoppe, Brooke organization: Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH) – sequence: 13 givenname: Nandini surname: Samanta fullname: Samanta, Nandini organization: Center for Immunology and Inflammatory Diseases, Department of Medicine, MGH, Krantz Family Center for Cancer Research, Department of Medicine, MGH, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard – sequence: 14 givenname: Sidney surname: Martin fullname: Martin, Sidney organization: Center for Immunology and Inflammatory Diseases, Department of Medicine, MGH, Krantz Family Center for Cancer Research, Department of Medicine, MGH, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard – sequence: 15 givenname: Alice surname: Tirard fullname: Tirard, Alice organization: Center for Immunology and Inflammatory Diseases, Department of Medicine, MGH, Krantz Family Center for Cancer Research, Department of Medicine, MGH, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard – sequence: 16 givenname: Benjamin Y. surname: Arnold fullname: Arnold, Benjamin Y. organization: Center for Immunology and Inflammatory Diseases, Department of Medicine, MGH, Krantz Family Center for Cancer Research, Department of Medicine, MGH, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard – sequence: 17 givenname: Jessica surname: Tantivit fullname: Tantivit, Jessica organization: Center for Immunology and Inflammatory Diseases, Department of Medicine, MGH, Krantz Family Center for Cancer Research, Department of Medicine, MGH, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard – sequence: 18 givenname: Joseph surname: Yarze fullname: Yarze, Joseph organization: Division of Gastroenterology, Department of Medicine, MGH – sequence: 19 givenname: Kyle surname: Staller fullname: Staller, Kyle organization: Division of Gastroenterology, Department of Medicine, MGH, Clinical and Translational Epidemiology Unit, MGH – sequence: 20 givenname: Daniel C. surname: Chung fullname: Chung, Daniel C. organization: Division of Gastroenterology, Department of Medicine, MGH – sequence: 21 givenname: Alexandra-Chloé orcidid: 0000-0001-7461-0408 surname: Villani fullname: Villani, Alexandra-Chloé organization: Center for Immunology and Inflammatory Diseases, Department of Medicine, 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) – sequence: 22 givenname: Slim surname: Sassi fullname: Sassi, Slim organization: Center for Computational and Integrative Biology, Massachusetts General Hospital (MGH), Harvard Medical School (HMS), Department of Orthopedic Surgery, MGH – sequence: 23 givenname: Hamed orcidid: 0000-0002-7956-6941 surname: Khalili fullname: Khalili, Hamed email: hkhalili@mgh.harvard.edu, hamed.khalili@ki.se organization: Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Division of Gastroenterology, Department of Medicine, MGH, Clinical and Translational Epidemiology Unit, MGH, Institute of Environmental Medicine, Nutrition Epidemiology, Karolinska Institutet |
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| Snippet | 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... 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... |
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| SubjectTerms | 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 |
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| Title | Single-cell transcriptomic characterization of microscopic colitis |
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