1. Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease
- Author
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Unen, V. van, Ouboter, L.F., Li, N., Schreurs, M., Abdelaal, T., Kooy-Winkelaar, Y., Beyrend, G., Hoellt, T., Maljaars, P.W.J., Mearin, M.L., Mahfouz, A., Witte, A.M.C., Clemens, C.H.M., Abraham, S., Escher, J.C., Lelieveldt, B.P.F., Pascutti, M.F., Jong, A.E.V.E. de, Koning, F., and Pediatrics
- Subjects
Inflammation ,Crohn’s disease ,mass cytometry ,Immunology ,CD8-Positive T-Lymphocytes ,intestinal immune cell network ,inflammatory bowel diseases ,Intestines ,Crohn's disease ,mucosal immunology ,Humans ,single-cell analysis ,Immunology and Allergy ,Colitis, Ulcerative ,CyTOF ,ulcerative colitis - Abstract
Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.
- Published
- 2022