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


ABSTRACT: The neurotransmitter ?-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.

SUBMITTER: Bhandage AK 

PROVIDER: S-EPMC5952354 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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

Bhandage Amol K AK   Jin Zhe Z   Korol Sergiy V SV   Shen Qiujin Q   Pei Yu Y   Deng Qiaolin Q   Espes Daniel D   Carlsson Per-Ola PO   Kamali-Moghaddam Masood M   Birnir Bryndis B  

EBioMedicine 20180328


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<sup>+</sup> 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<sup>+</sup> T cells from ND indiv  ...[more]

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