PD-1high memory-phenotype CD4 T cells mediate type 2 bystander immunity and promote pulmonary fibrosis via BATF/amphiregulin axis

Single-cell RNA sequencing(scRNA-seq) was performed to investigate the differentiation process of steady-state CD4 T cells following treatmernt with IL-25 and IL-33, after initial isolation via FACS. This analysis revealed that steady-state PD-1high CD4 T cell differentiate into patogenic Th2 cells, characterized by the expression of IL-13, IL-5 and amphireguling. These findings suggest that steady-state PD-1high CD4 T cells may contribute to pulmonary fibrosis through its differntiation into pathogenic Th2 cells. This dataset includes previously published scRNA-seq data from [Min-Ji Cho et al., 2023] To investigate the tissue-specific roles of Pdcd1 in CD4⁺ T cells, bulk RNA sequencing was performed on Pdcd1^high and Pdcd1^low CD4⁺ T cells isolated from the spleen and lungs of mice. Differential gene expression analysis revealed that Pdcd1^high CD4⁺ T cells in both tissues were enriched for Th2- and fibrosis-related gene signatures. Notably, chemokine receptor expression profiles differed between spleen and lung, suggesting tissue-specific transcriptional programs associated with Pdcd1 expression.