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.

中文翻译：

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狼疮易感基因 Pbx1 通过 Rtkn2 表达控制调节性 T 细胞的发育、稳定性和功能

维持监管T（T注册）细胞严重阻止自身免疫。前B细胞白血病转录因子1（PBx1) 变异与狼疮易感性相关，特别是通过显性失活亚型的表达PBX1-d在CD4中+T细胞。PBX1-d过度表达损害T注册细胞稳态并促进炎症 CD4+T细胞。在这里，我们展现了高度的表达PBx1在人类和小鼠 T注册狼疮患者和小鼠体内的细胞减少。PBx1缺乏或PBX1-d过度表达降低了 T 的数量、稳定性和抑制活性注册细胞，这增加了小鼠对免疫和自身免疫诱导的反应。从机械上来说，PBx1缺乏改变了T细胞中与细胞周期和凋亡有关的基因的表达注册细胞。有趣的是，Rtkn2，一种先前与 T 相关的 Rho-GTPase注册稳态，直接被 Pbx1 反式激活。我们的结果表明，维持 T注册细胞稳态和稳定性PBx1通过细胞周期进展防止炎症 T 细胞的扩张，否则会加剧宿主狼疮的进展。