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Paxbp1 is indispensable for the survival of CD4 and CD8 double-positive thymocytes.

Authors :
Wenting Li
Yang Yang
Shenglin Liu
Dongsheng Zhang
Xuanyao Ren
Mindan Tang
Wei Zhang
Xiaofan Chen
Cong Huang
Bo Yu
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]

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