| First Author | Shi N | Year | 2023 |
| Journal | Immunobiology | Volume | 228 |
| Issue | 5 | Pages | 152461 |
| PubMed ID | 37515879 | Mgi Jnum | J:354571 |
| Mgi Id | MGI:7735043 | Doi | 10.1016/j.imbio.2023.152461 |
| Citation | Shi N, et al. (2023) RNA-Seq and ATAC-Seq analyses reveal a global transcriptional and chromatin accessibility profiling of gammadelta T17 differentiation from mouse spleen. Immunobiology 228(5):152461 |
| abstractText | IL-17A-producing gammadelta T cells (gammadelta T17) are known to play important roles in various autoimmune diseases. However, the molecular mechanisms of gammadelta T17 differentiation and their functions have not been clarified yet. Here, we sorted IL-17A(+) Vgamma4, IL-17A(-) Vgamma4, and Vgamma1 subsets from mouse spleen by in vitro priming of gammadelta 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 gammadelta T17. We identified key modules and MCODEs involved in the control of IL-17A(+) Vgamma4, IL-17A(-) Vgamma4, and Vgamma1 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 gammadelta T17 differentiation. Simultaneously, we conducted chromatin accessibility profiling under gammadelta T17 differentiation by ATAC-seq. The top six candidate genes were screened for gammadelta T17 differentiation and function by integrating RNA-seq and ATAC-seq analysis, and the results were further confirmed using RT-qPCR, flow cytometry, and western blot. In addition, the 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 gammadelta T17 differentiation and function and may improve to the development of therapeutic approaches or drugs targeting gammadelta T17 for autoimmune diseases. |
