Single-cell analysis pinpoints distinct populations of cytotoxic CD4+ T cells and an IL-10+CD109+ TH2 cell population in nasal polyps

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a chronic inflammatory process often associated with comorbid asthma. In this study, we analyzed the transcriptomes of single T helper (T_H) cells from nasal polyps of patients with CRSwNP and validated these findings using multiparameter flow cytometry. Polyp tissue contained suppressive T regulatory (T_reg) cells, T_H2 cells, type 2 innate lymphoid cells, and three transcriptionally distinct subsets of cytotoxic CD4⁺ T cells (CD4⁺ CTL). GATA3 expression was a feature of polyp T_reg cells, whereas T_H2 cells highly expressed TCN1, CD200R, and HPGDS and were enriched for genes involved in lipid metabolism. Only a portion of polyp T_H2 cells expressed the prostaglandin D2 receptor CRTH2, whereas a subpopulation of CD109⁺CRTH2^- T_H2 cells expressed mRNA for common inhibitor receptors including LAG3 and TIM3 and produced IL-10. Together, we resolved the complexity of T_H cells in patients with CRSwNP, identifying several distinct clusters of CD4⁺ CTL and a population of CD109⁺CRTH2^- T_H2 cells with putative regulatory potential.