GSE121284
Molecular and functional heterogeneity of IL-10-producing CD4+ T cells [Mouse Bulk-seq]
IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4+ T cells are phenotypically and functionally heterogeneous. By combining single cell transcriptome and functional analyses, we identified a subpopulation of IL-10-producing Foxp3Neg CD4+ T cells that displays regulatory activity unlike other IL-10-producing CD4+ T cells, which are unexpectedly pro-inflammatory. The combinatorial expression of co-inhibitory receptors is sufficient to discriminate IL-10-producing CD4+ T cells with regulatory function from others and to identify them across different tissues and disease models in mice and humans. These regulatory IL-10-producing Foxp3Neg CD4+ T cells have a unique transcriptional program, which goes beyond the regulation of IL-10 expression. Finally, we found that patients with Inflammatory Bowel Disease (IBD), demonstrate a deficiency in this specific regulatory T-cell subpopulation. Overall design: We carried out high troughput RNA sequencing of RNA isolated from IL-10 producing Foxp3- CD4+ T-cells, which were isolated from the spleen of mice treated with anti-CD3 antibody.