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Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease
Vanessa Mitsialis, Sarah Wall, Peng Liu, Jose Ordovas-Montanes, Tamar Parmet, Marko Vukovic, Dennis Spencer, Michael Field, Collin McCourt, Jessica Toothaker Athos Bousvaros, BCH IBD Center, BWH Crohn’s and Colitis Center, Alex K. Shalek, Leslie Kean, Bruce Horwitz, Jeffrey Goldsmith, George Tseng, Scott B. Snapper and Liza Konnikova
Background & Aims: Studies are needed to determine the mechanisms of mucosal dysregulation in
patients with inflammatory bowel diseases (IBD) and differences in inflammatory responses of patients
with ulcerative colitis (UC) vs Crohn’s disease (CD). We used mass cytometry (CyTOF) to characterize and
compare immune cell populations in the mucosa and blood from patients with IBD and without IBD
(controls) at single-cell resolution.
Methods: We performed CyTOF analysis of colonic mucosa samples (n=87) and peripheral blood
mononuclear cells (PBMCs, n=85) from patients with active or inactive UC or CD and controls. We also
performed single-cell RNA-sequencing, flow cytometry, and RNA in situ hybridization analyses to
validate key findings. We used random forest modeling to identify differences in signatures across
Results: Compared with controls, colonic mucosa samples from patients with IBD had increased
abundances of HLA-DR+CD38+ T cells, including T-regulatory cells that produce inflammatory cytokines;
CXCR3+ plasmablasts; and IL1B+ macrophages and monocytes. Colonic mucosa samples from patients
with UC were characterized by expansion of IL17A+ CD161+ effector memory T cells and IL17A+ Tregulatory cells; expansion of HLA-DR+CD56+ granulocytes; and reductions in type 3 innate lymphoid
cells. Mucosal samples from patients with active CD were characterized by IL1B+HLA-DR+CD38+ T cells,
IL1B+TNF+IFNG+ naïve B cells, IL1B+ dendritic cells (DCs), and IL1B+ plasmacytoid DCs. PBMCs from
patients with active CD differed from those of active UC in that the PBMCs from patients with CD had
increased IL1B+ T-regulatory cells, IL1B+ DCs and IL1B+ plasmacytoid DCs, IL1B+ monocytes, and fewer
group 1 innate lymphoid cells. Random forest modeling differentiated active UC from active CD in
colonic mucosa and blood samples; top discriminating features included many of the cellular
populations identified above.
Conclusions: We used single-cell technologies to identify immune cell populations specific to mucosa
and blood samples from patients with active or inactive CD and UC and controls. This information might
be used to develop therapies that target specific cell populations in patients with different types of IBD.