Single-cell analyses of Crohn’s disease tissues reveal intestinal intraepithelial T cells heterogeneity and altered subset distributions
Year: 2021
Type: article
Study design: Observational Study
Abstract: Crohn’s disease (CD) is a chronic transmural inflammation of intestinal segments caused by dysregulated interaction between microbiome and gut immune system. Here, we profile, via multiple single-cell technologies, T cells purified from the intestinal epithelium and lamina propria (LP) from terminal ileum resections of adult severe CD cases. We find that intraepithelial lymphocytes (IEL) contain several unique T cell subsets, including NKp30 + γδT cells expressing RORγt and producing IL-26 upon NKp30 engagement. Further analyses comparing tissues from non-inflamed and inflamed regions of patients with CD versus healthy controls show increased activated T H 17 but decreased CD8 + T, γδT, T FH and Treg cells in inflamed tissues. Similar analyses of LP find increased CD8 + , as well as reduced CD4 + T cells with an elevated T H 17 over Treg/T FH ratio. Our analyses of CD tissues thus suggest a potential link, pending additional validations, between transmural inflammation, reduced IEL γδT cells and altered spatial distribution of IEL and LP T cell subsets.
Source: Nature Communications
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: U.S. Department of Health and Human Services, Institute of Clinical and Translational Sciences, Crohn's and Colitis Foundation, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Dental and Craniofacial Research, National Center for Advancing Translational Sciences
Awards: G1290568931, G2289624923, G2824222223, G2983694025, G3324453019, G3455473179, G3892911239, G444632500, G4864870097, G5208357637, Mucosal Immune Defense Mechanisms of the Urinary Bladder, G5387316129, Modulation of Lung Immune Responses to Viral Infection, Systematic dissection of gut cellular circuits [at single cell resolution], G6825781856, Plasticity of Innate Lymphoid Cells: Mechanisms and Biological Impact, G8660027208, G9000029463, G9000037442, G9000048633, G9000095412, G9000117408, G9000189848, G9000336379, Cis-Regulatory Circuits for ILC Function and Plasticity, Washington University Rheumatic Diseases Research Resource-based Center, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital
OpenAlex ID: W3137742875