Elucidation of suppressive mechanisms of autoreactive B cells byCD4+CD25-LAG3+ regulatory T cells

本项目的目的是阐明表达Egr2的CD4+CD25-LAG3+调节性T细胞(LAG3Treg)在调节自身抗体产生中的作用。将LAG3Treg从对照MRL/+小鼠过继转移到MRL/Faslpr狼疮易感小鼠，显著抑制了肾炎的进展和自身抗体的产生。有趣的是，LAG3Treg共表达Egr2和PD-L1，来自T细胞特异性Egr2条件性基因敲除或PD1基因敲除小鼠的LAG3Treg未能抑制B细胞抗体的产生。这些结果表明，LAG3Treg通过Fas/FasL和PD-1/PD-L1相互作用，在阻止B细胞过度反应中发挥重要作用。通过开发LAG3+Tregs的能力，它们可能为包括SLE在内的自身抗体介导的自身免疫性疾病提供一种新的治疗方法。

The aim of this project is to elucidate the role of Egr2-expressing CD4+CD25-LAG3+ regulatory T cells (LAG3 Treg) in regulation of autoantibody production. Adoptive transfer of LAG3 Treg from control MRL/+ mice to MRL/Faslpr lupus prone mice significantly suppressed the progression of nephritis and autoantibody production. Interestingly, LAG3 Treg co-expressed Egr2 and PD-L1, and LAG3 Treg from T-cell-specific Egr2 conditional knockout or PD1 knockout mice failed to suppress B cell antibody production. These findings elucidate that LAG3 Treg play a crucial role in preventing the excessive B cell responses via Fas/FasL and PD-1/PD-L1 interactions. By exploiting the capacity of LAG3+ Tregs, they may provide a new therapeutic method in autoantibody-mediated autoimmune diseases, including SLE.