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

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.