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Sci. Adv., Mar 29 2024, 10 (13) | https://doi.org/10.1126/sciadv.adi4310
Lupus susceptibility gene Pbx1 controls the development, stability, and function of regulatory T cells via Rtkn2 expression
Seung- Chul Choi1, Yuk Pheel Park1, Tracoyia Roach1, Damian Jimenez1, Amanda Fisher1, Mojgan Zadeh1, Longhuan Ma1, Eric S. Sobel2, Yong Ge1, Mansour Mohamadzadeh1, Laurence Morel1*
1Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health San Antonio, TX 78229-3900, USA.
2Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
*Corresponding author : Laurence Morel
Abstract
The maintenance of regulatory T (T
reg) 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 T
reg cell homeostasis and promoted inflammatory CD4
+ T cells. Here, we showed a high expression of
Pbx1 in human and murine T
reg cells, which is decreased in lupus patients and mice.
Pbx1 deficiency or
Pbx1-d overexpression reduced the number, stability, and suppressive activity of T
reg 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 T
reg cells. Intriguingly,
Rtkn2, a Rho-GTPase previously associated with T
reg homeostasis, was directly transactivated by Pbx1. Our results suggest that the maintenance of T
reg 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.
논문정보
- Research article
- 2024년 03월 (BRIC 등록일 2024-03-29)
- 국외 연구진
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