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GABA 调节外周血单个核细胞和 CD4 T 细胞中炎症细胞因子的释放，并在 1 型糖尿病中具有免疫抑制作用。

GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4 T Cells and Is Immunosuppressive in Type 1 Diabetes.

机构信息

Department of Neuroscience, Uppsala University, 75124 Uppsala, Sweden.

Department of Immunology, Genetics and Pathology, Science for Life laboratory, Uppsala University, 75124 Uppsala, Sweden.

出版信息

EBioMedicine. 2018 Apr;30:283-294. doi: 10.1016/j.ebiom.2018.03.019. Epub 2018 Mar 28.

DOI:10.1016/j.ebiom.2018.03.019
PMID:29627388
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5952354/
Abstract

The neurotransmitter γ-aminobutyric acid (GABA) is an extracellular signaling molecule in the brain and in pancreatic islets. Here, we demonstrate that GABA regulates cytokine secretion from human peripheral blood mononuclear cells (PBMCs) and CD4 T cells. In anti-CD3 stimulated PBMCs, GABA (100nM) inhibited release of 47 cytokines in cells from patients with type 1 diabetes (T1D), but only 16 cytokines in cells from nondiabetic (ND) individuals. CD4 T cells from ND individuals were grouped into responder or non-responder T cells according to effects of GABA (100nM, 500nM) on the cell proliferation. In the responder T cells, GABA decreased proliferation, and inhibited secretion of 37 cytokines in a concentration-dependent manner. In the non-responder T cells, GABA modulated release of 8 cytokines. GABA concentrations in plasma from T1D patients and ND individuals were correlated with 10 cytokines where 7 were increased in plasma of T1D patients. GABA inhibited secretion of 5 of these cytokines from both T1D PBMCs and ND responder T cells. The results identify GABA as a potent regulator of both Th1- and Th2-type cytokine secretion from human PBMCs and CD4 T cells where GABA generally decreases the secretion.

摘要

神经递质 γ-氨基丁酸（GABA）是大脑和胰腺胰岛中的细胞外信号分子。在这里，我们证明 GABA 调节人外周血单核细胞（PBMC）和 CD4 T 细胞中的细胞因子分泌。在抗 CD3 刺激的 PBMC 中，GABA（100nM）抑制 1 型糖尿病（T1D）患者细胞中 47 种细胞因子的释放，但仅抑制非糖尿病（ND）个体细胞中 16 种细胞因子的释放。根据 GABA（100nM，500nM）对细胞增殖的影响，将 ND 个体的 CD4 T 细胞分为应答者或非应答者 T 细胞。在应答者 T 细胞中，GABA 以浓度依赖的方式降低增殖，并抑制 37 种细胞因子的分泌。在非应答者 T 细胞中，GABA 调节 8 种细胞因子的释放。T1D 患者和 ND 个体血浆中的 GABA 浓度与 10 种细胞因子相关，其中 7 种在 T1D 患者的血浆中增加。GABA 抑制这两种 T1D PBMC 和 ND 应答者 T 细胞中 5 种细胞因子的分泌。研究结果表明，GABA 是人类 PBMC 和 CD4 T 细胞中 Th1 和 Th2 型细胞因子分泌的有效调节剂，GABA 通常会减少细胞因子的分泌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/26db7fc4ebd9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/c2cf64b4d802/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/3f9ea54b0f41/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/869810106249/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/c63450ee7125/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/26db7fc4ebd9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/c2cf64b4d802/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/3f9ea54b0f41/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/869810106249/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/c63450ee7125/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d198/5952354/26db7fc4ebd9/gr5.jpg

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