Unknown

Dataset Information

0

Lupus susceptibility gene Pbx1 controls the development, stability, and function of regulatory T cells via Rtkn2 expression.

ABSTRACT: The maintenance of regulatory T (Treg) cells critically prevents autoimmunity. Pre-B cell leukemia transcription factor 1 (Pbx1) variants are associated with lupus susceptibility, particularly through the expression of a dominant negative isoform Pbx1-d in CD4+ T cells. Pbx1-d overexpression impaired Treg cell homeostasis and promoted inflammatory CD4+ T cells. Here, we showed a high expression of Pbx1 in human and murine Treg cells, which is decreased in lupus patients and mice. Pbx1 deficiency or Pbx1-d overexpression reduced the number, stability, and suppressive activity of Treg cells, which increased murine responses to immunization and autoimmune induction. Mechanistically, Pbx1 deficiency altered the expression of genes implicated in cell cycle and apoptosis in Treg cells. Intriguingly, Rtkn2, a Rho-GTPase previously associated with Treg homeostasis, was directly transactivated by Pbx1. Our results suggest that the maintenance of Treg cell homeostasis and stability by Pbx1 through cell cycle progression prevent the expansion of inflammatory T cells that otherwise exacerbates lupus progression in the hosts.

SUBMITTER: Choi SC 

PROVIDER: S-EPMC10971436 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Lupus susceptibility gene <i>Pbx1</i> controls the development, stability, and function of regulatory T cells via <i>Rtkn2</i> expression.

Choi Seung-Chul SC   Park Yuk Pheel YP   Roach Tracoyia T   Jimenez Damian D   Fisher Amanda A   Zadeh Mojgan M   Ma Longhuan L   Sobel Eric S ES   Ge Yong Y   Mohamadzadeh Mansour M   Morel Laurence L  

Science advances 20240327 13

The maintenance of regulatory T (T<sub>reg</sub>) cells critically prevents autoimmunity. Pre-B cell leukemia transcription factor 1 (<i>Pbx1</i>) variants are associated with lupus susceptibility, particularly through the expression of a dominant negative isoform <i>Pbx1-d</i> in CD4<sup>+</sup> T cells. <i>Pbx1-d</i> overexpression impaired T<sub>reg</sub> cell homeostasis and promoted inflammatory CD4<sup>+</sup> T cells. Here, we showed a high expression of <i>Pbx1</i> in human and murine T<  ...[more]

Similar Datasets

Unknown The PBX1 lupus susceptibility gene regulates CD44 expression.
| S-EPMC5389453 | biostudies-literature
Unknown The Lupus Susceptibility Gene Pbx1 Regulates the Balance between Follicular Helper T Cell and Regulatory T Cell Differentiation.
| S-EPMC4935607 | biostudies-literature
Unknown The transcription factor NFIL3 controls regulatory T-cell function and stability.
| S-EPMC6802641 | biostudies-literature
Unknown A PBX1 transcriptional network controls dopaminergic neuron development and is impaired in Parkinson's disease.
| S-EPMC5282836 | biostudies-literature
Transcriptomics Lupus susceptibility gene Esrrg regulates TREG development and suppressive function through mitochondrial metabolism
2020-09-01 | GSE150187 | GEO
Unknown SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation.
| S-EPMC6082899 | biostudies-literature
Transcriptomics Potentiation of regulatory T cell stability and function via a neuropilin-1:semaphorin-4a axis
2013-09-06 | E-GEOD-41185 | biostudies-arrayexpress
Unknown Lupus susceptibility gene Esrrg modulates regulatory T cells through mitochondrial metabolism.
| S-EPMC8410062 | biostudies-literature
Transcriptomics Pre-B cell leukemia homeobox protein Pbx1 is associated with lupus susceptibility in mice and humans
2010-06-16 | GSE22313 | GEO
Unknown Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.
| S-EPMC7710299 | biostudies-literature