Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease

• Published in: Frontiers in immunology Vol. 13; p. 893803
• Main Authors: van Unen, Vincent, Ouboter, Laura F., Li, Na, Schreurs, Mette, Abdelaal, Tamim, Kooy-Winkelaar, Yvonne, Beyrend, Guillaume, Höllt, Thomas, Maljaars, P. W. Jeroen, Mearin, M. Luisa, Mahfouz, Ahmed, Witte, Anne M. C., Clemens, Cornelis H. M., Abraham, Sunje, Escher, Johanna C., Lelieveldt, Boudewijn P. F., Pascutti, M. Fernanda, van der Meulen – de Jong, Andrea E., Koning, Frits
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 23.06.2022
• Subjects: Crohn’s disease; Immunology; inflammatory bowel diseases; intestinal immune cell network; mass cytometry; single-cell analysis; ulcerative colitis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.893803

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.