SRSF1 Deficiency Impairs the Late Thymocyte Maturation and the CD8 Single-Positive Lineage Fate Decision
| Autor: | Ce Ji, Li Bao, Shunzong Yuan, Zhihong Qi, Fang Wang, Menghao You, Guotao Yu, Jingjing Liu, Xiao Cui, Zhao Wang, Juanjuan Liu, Wenhui Guo, Mingxia Feng, Feng Chen, Youmin Kang, Shuyang Yu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Thymocytes
Serine-Arginine Splicing Factors Immunology thymocyte Down-Regulation Cell Differentiation Mice Transgenic RC581-607 CD8-Positive T-Lymphocytes Lymphocyte Activation Hematopoiesis SRSF1 Mice Inbred C57BL Mice Core Binding Factor Alpha 3 Subunit Gene Expression Regulation Runx3 CD4 Antigens lineage choice Immunology and Allergy Animals Cell Lineage Immunologic diseases. Allergy CD8+ T cell development |
| Zdroj: | Frontiers in Immunology, Vol 13 (2022) |
| ISSN: | 1664-3224 |
| Popis: | 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 ofRunx3, 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|