RNA-Seq and ATAC-Seq analyses reveal a global transcriptional and chromatin accessibility profiling of gdT17 differentiation from mouse spleen. Mus musculus

IL-17A-producing gd T cells (gd T17) are known to play important roles in various autoimmune diseases. However, the molecular mechanisms of gd T17 differentiation and their functions have not been clarified yet. Here, we sorted IL-17A+ Vg4, IL-17A- Vg4, and Vg1 subsets from mouse spleen by in vitro priming of gd T17 cells and investigated their differentially expressed genes (DEGs) and differentially accessible regions (DARs) using RNA-seq and ATAC-seq, respectively. Our results showed that DEGs-1 (upregulated genes: 677 and downregulated genes: 821) and DEGs-2 (upregulated genes: 1188 and downregulated genes: 1252) were most closely related to the function and differentiation of peripheral gd T17. We identified key modules and MCODEs involved in the control of IL-17A+ Vg4, IL-17A- Vg4, and Vg1 subsets using the WGCNA and Metascape analysis. Furthermore, 26 key transcription factors were enriched in three subsets, which contributed to deciphering the potential molecular mechanism driving gd T17 differentiation. Simultaneously, we conducted chromatin accessibility profiling under gd T17 differentiation by ATAC-seq. The top six candidate genes were screened for gd T17 differentiation and function by integrating RNA-seq and ATAC-seq analysis, and the results were further confirmed using RT-qPCR. In addition, association analysis of candidate genes with the RNA-seq database of psoriasis was performed to elucidate the functional relationship. Our findings provided a novel insight into understanding the molecular mechanisms of gd T17 differentiation and function and may improve to the development of therapeutic approaches or drugs targeting gd T17 for autoimmune diseases.