Cell-by-cell deciphering of T cells in allergic inflammation

Technical advances in single-cell RNA sequencing (scRNA-seq) render it possible to examine the transcriptomes of single cells in patients with allergic inflammation with high resolution in the context of their specific microenvironment, treatment, and disease status. Using a recently published scRNA-seq study of tissue T cells as an example, we introduce the major pipeline steps, illustrate the options of scRNA-seq platforms, summarize new knowledge gained from this study, and provide directions for future research. The presented scRNA-seq study elucidated the T-cell heterogeneity present in an allergic inflammatory tissue focused on eosinophilic esophagitis, a prototypic, chronic, allergic disease, which provided a unique opportunity to probe the pathogenesis of allergic inflammation at the tissue level through readily available endoscopically procured biopsy specimens. scRNA-seq analysis identified 8 populations of CD3⁺ T cells and defined 2 disease-specific populations of CD3⁺CD4⁺ T cells, including a markedly activated type 2 cytokine-producing pathogenic cell population distinguished by expression of the short-chain fatty acid receptor free fatty acid receptor 3 and a population of regulatory T cells. In addition to presenting and interpreting new findings within the prior literature, we postulate about future single-cell next-generation sequencing platforms in this burgeoning field.