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Paxbp1 is indispensable for the survival of CD4 and CD8 double-positive thymocytes.
- Source :
- Frontiers in Immunology; 2023, p1-14, 14p
- Publication Year :
- 2023
-
Abstract
- The lifespan of double-positive (DP) thymocytes is critical for intrathymic development and shaping the peripheral T cell repertoire. However, the molecular mechanisms that control DP thymocyte survival remain poorly understood. Paxbp1 is a conserved nuclear protein that has been reported to play important roles in cell growth and development. Its high expression in T cells suggests a possible role in T cell development. Here, we observed that deletion of Paxbp1 resulted in thymic atrophy in mice lacking Paxbp1 in the early stages of T cell development. Conditional loss of Paxbp1 resulted in fewer CD4<superscript>+</superscript>CD8<superscript>+</superscript> DP T cells, CD4 and CD8 single positive (SP) T cells in the thymus, and fewer T cells in the periphery. Meanwhile, Paxbp1 deficiency had limited effects on the CD4<superscript>-</superscript> CD8<superscript>-</superscript> double negative (DN) or immature single-positive (ISP) cell populations. Instead, we observed a significant increase in the susceptibility of Paxbp1-deficient DP thymocytes to apoptosis. Consistent with this, RNA-Seq analysis revealed a significant enrichment of the apoptotic pathway within differentially expressed genes in Paxbp1-deficient DP cells compared to control DP cells. Together, our results suggest a new function for Paxbp1, which is an important mediator of DP thymocyte survival and critical for proper thymic development. [ABSTRACT FROM AUTHOR]
- Subjects :
- THYMOCYTES
CD8 antigen
T cells
CD4 antigen
CELL populations
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Database :
- Complementary Index
- Journal :
- Frontiers in Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 164714730
- Full Text :
- https://doi.org/10.3389/fimmu.2023.1183367