Identification of ulcerative colitis-specific immune cell signatures from public single-cell RNA-seq data

Abstract

Background: Single-cell RNA-seq enabled microscopic studies on tissue microenvironment of many diseases. Inflammatory bowel disease, an autoimmune disease, is involved with various dysfunction of immune cells, for which single-cell RNA-seq may provide us a deeper insight into the causes and mechanism of this complex disease.

Objective: In this work, we used public single-cell RNA-seq data to study tissue microenvironment around ulcerative colitis, an inflammatory bowel disease causing chronic inflammation and ulcers in large intestine.

Methods: Since not all the datasets provide cell-type annotations, we first identified cell identities to select cell populations of our interest. Differentially expressed genes and gene set enrichment analysis was then performed to infer the polarization/activation state of macrophages and T cells. Cell-to-cell interaction analysis was also performed to discover distinct interactions in ulcerative colitis.

Results: Differentially expressed genes analysis of the two datasets confirmed the regulation of CTLA4, IL2RA, and CCL5 genes in the T cell subset and regulation of S100A8/A9, CLEC10A genes in macrophages. Cell-to-cell interaction analysis showed CD4⁺ T cells and macrophages interact actively to each other. We also identified IL-18 pathway activation in inflammatory macrophages, evidence that CD4⁺ T cells induce Th1 and Th2 differentiation, and also found that macrophages regulate T cell activation through different ligand-receptor pairs, viz. CD86-CTL4, LGALS9-CD47, SIRPA-CD47, and GRN-TNFRSF1B.

Conclusion: Analysis of these immune cell subsets may suggest novel strategies for the treatment of inflammatory bowel disease.

Keywords: Immune cell signature; Inflammatory bowel disease; Single-cell RNA-seq; Ulcerative colitis.