| First Author | Ji C | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 838719 | PubMed ID | 35154164 |
| Mgi Jnum | J:321580 | Mgi Id | MGI:6875885 |
| Doi | 10.3389/fimmu.2022.838719 | Citation | Ji C, et al. (2022) SRSF1 Deficiency Impairs the Late Thymocyte Maturation and the CD8 Single-Positive Lineage Fate Decision. Front Immunol 13:838719 |
| abstractText | The underlying mechanisms of thymocyte development and lineage determination remain incompletely understood, and the emerging evidences demonstrated that RNA binding proteins (RBPs) are deeply involved in governing T cell fate in thymus. Serine/arginine-rich splicing factor 1 (SRSF1), as a classical splicing factor, is a pivotal RBP for gene expression in various biological processes. Our recent study demonstrated that SRSF1 plays essential roles in the development of late thymocytes by modulating the T cell regulatory gene networks post-transcriptionally, which are critical in response to type I interferon signaling for supporting thymocyte maturation. Here, we report SRSF1 also contributes to the determination of the CD8(+) T cell fate. By specific ablation of SRSF1 in CD4(+)CD8(+) double positive (DP) thymocytes, we found that SRSF1 deficiency impaired the maturation of late thymocytes and diminished the output of both CD4(+) and CD8(+) single positive T cells. Interestingly, the ratio of mature CD4(+) to CD8(+) cells was notably altered and more severe defects were exhibited in CD8(+) lineage than those in CD4(+) lineage, reflecting the specific function of SRSF1 in CD8(+) T cell fate decision. Mechanistically, SRSF1-deficient cells downregulate their expression of Runx3, which is a crucial transcriptional regulator in sustaining CD8(+) single positive (SP) thymocyte development and lineage choice. Moreover, forced expression of Runx3 partially rectified the defects in SRSF1-deficient CD8(+) thymocyte maturation. Thus, our data uncovered the previous unknown role of SRSF1 in establishment of CD8(+) cell identity. |
