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+ 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.
Duke Scholars
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Related Subject Headings
- Transcriptome
- T-Lymphocytes, Regulatory
- Single-Cell Analysis
- Mice, Inbred C57BL
- Mice
- Male
- Intestinal Mucosa
- Interleukin-10
- Humans
- Gene Expression Profiling
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Transcriptome
- T-Lymphocytes, Regulatory
- Single-Cell Analysis
- Mice, Inbred C57BL
- Mice
- Male
- Intestinal Mucosa
- Interleukin-10
- Humans
- Gene Expression Profiling