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

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.

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@article{ bib:2022_front_immunol,
    author = {Vincent van Unen and Laura F. Ouboter and Na Li and Mette Schreurs and Tamim Abdelaal and Yvonne Kooy-Winkelaar and Guillaume Beyrend and Thomas H{\"o}llt and P. W. Jeroen Maljaars and M. Luisa Mearin and Ahmed Mahfouz and Anne M. C. Witte and Cornelis H. M. Clemens and Sunje Abraham and Johanna C. Escher and Boudewijn Lelieveldt and M. Fernanda Pascutti and Andrea E. van der Meulen – de Jong and Frits Koning},
    title = { Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease },
    journal = { Frontiers in Immunology },
    volume = { 12 },
    year = { 2022 },
    doi = { 10.3389/fimmu.2022.893803 },
}