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

阐明 CD4 CD25-LAG3 调节性 T 细胞对自身反应性 B 细胞的抑制机制

• 批准号: 23791106
• 负责人: OKAMURA Tomohisa
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791106/
• 关键词: 制御性T細胞; 自己抗体; 全身性エリテマトーデス; LAG3; Egr2

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.

本项目的目的是阐明表达Egr 2的CD 4 + CD 25-LAG 3+调节性T细胞（LAG 3 Treg）在调节自身抗体产生中的作用。LAG 3 Treg从对照MRL/+小鼠向MRL/Faslpr狼疮易感小鼠的连续转移显著抑制了肾炎和自身抗体产生的进展。有趣的是，LAG 3 Treg共表达Egr 2和PD-L1，并且来自T细胞特异性Egr 2条件性敲除或PD 1敲除小鼠的LAG 3 Treg未能抑制B细胞抗体产生。这些发现阐明了LAG 3 Treg通过Fas/FasL和PD-1/PD-L1相互作用在防止过度的B细胞应答中起关键作用。通过利用LAG 3 + THBE的能力，他们可能为自身抗体介导的自身免疫性疾病（包括SLE）提供新的治疗方法。

项目成果

Egr2 and Egr3 are the unique regulators for systemic autoimmunity.

• DOI: 10.4161/jkst.23952
• 发表时间: 2013-04-01
• 期刊: JAK-STAT
• 作者: Sumitomo S;Fujio K;Okamura T;Yamamoto K
• 通讯作者: Yamamoto K

"DEVELOPMENT OF AUTOANTIBODY SUPPRESSIVE EGR2 EXPRESSING CD4+CD25-LAG3+ REGULATORY T CELLS IS DEPENDENT ON FAS-FAS LIGAND INTERACTION"

“表达 CD4 CD25-LAG3 调节性 T 细胞的自身抗体抑制 EGR2 的发育依赖于 FAS-FAS 配体相互作用”

• 发表时间: 2012
• 作者: Shuji Sumitomo;Keishi Fujio;Tomohisa Okamura and Kazuhiko Yamamoto;Tomohisa Okamura;Tomohisa Okamura
• 通讯作者: Tomohisa Okamura