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Lkb1 在树突状细胞中限制体内 CD8Foxp3regulatory T 细胞的扩增。

Lkb1 in dendritic cells restricts CD8Foxp3regulatory T cells expansion in vivo.

机构信息

Fujian Medical University, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China.

State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China.

出版信息

Exp Cell Res. 2019 Nov 15;384(2):111650. doi: 10.1016/j.yexcr.2019.111650. Epub 2019 Sep 26.

Abstract

Liver kinase B1 (Lkb1) in dendritic cells (DCs) plays a key role in maintaining immunity homeostasis and adaptive immunity by controlling the CD4Foxp3T regulatory cell (CD4Tregs) pool and T cells activation. However, the function of Lkb1 in DCs for the regulation of CD8Foxp3T regulatory cells (CD8Tregs) has not been addressed. Herein, we found that Lkb1-deficient DCs could lead to excessive CD8Tregs expansion in multiple organs. We found that OX40 expression was significantly higher in Lkb1-deficient DCs compared with that in wild-type (WT) mice, suggesting a potential pathway of CD8Treg expansion. Moreover, we found that CD8Tregs from mice with conditional deletion Lkb1 in DCs (KO) displayed an activated phenotype and expressed higher levels of specific markers, including ICOS and CD103. Interestingly, compared with the WT mice without lipopolysaccharide(LPS) treatment, we found that CD8Tregs population increased in the WT mice with LPS treatment which can selectively delete Lkb1 protein in DCs. However, there was no significant difference in CD8Tregs population in the KO mice between LPS treatment group and non-LPS treatment. Collectively, our findings identified Lkb1 in DCs as a crucial regulator of CD8Treg expansion.

摘要

肝激酶 B1(Lkb1)在树突状细胞(DC)中通过控制 CD4Foxp3T 调节性细胞(CD4Tregs)池和 T 细胞激活,对于维持免疫稳态和适应性免疫起着关键作用。然而,Lkb1 在 DC 中对 CD8Foxp3T 调节性细胞(CD8Tregs)的调节功能尚未得到解决。在此,我们发现 Lkb1 缺陷型 DC 可导致多个器官中 CD8Tregs 的过度扩增。我们发现,与野生型(WT)小鼠相比,Lkb1 缺陷型 DC 中 OX40 的表达明显升高,提示 CD8Treg 扩增的潜在途径。此外,我们发现,来自 DC 中条件性删除 Lkb1 的小鼠(KO)的 CD8Tregs 表现出激活表型,并表达更高水平的特异性标记物,包括 ICOS 和 CD103。有趣的是,与未经脂多糖(LPS)处理的 WT 小鼠相比,我们发现经 LPS 处理的 WT 小鼠中 CD8Tregs 群体增加,而 LPS 处理可选择性地删除 DC 中的 Lkb1 蛋白。然而,在 LPS 处理组和非 LPS 处理组之间,KO 小鼠中的 CD8Tregs 群体没有明显差异。总之,我们的研究结果确定了 DC 中的 Lkb1 是 CD8Treg 扩增的关键调节因子。

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