GABA Regulates Release of Inflammatory Cytokines From Peripheral Blood Mononuclear Cells and CD4+ T Cells and Is Immunosuppressive in Type 1 DiabetesShow others and affiliations
2018 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 30, p. 283-294Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
2018. Vol. 30, p. 283-294
Keywords [en]
PBMCs, Immune cells, Proliferation, Cytokine, GABAA receptor, Diabetes, T1D, Autoimmune disease, T cell
National Category
Other Medical Sciences not elsewhere specified Endocrinology and Diabetes
Research subject
Biology; Physiology
Identifiers
URN: urn:nbn:se:uu:diva-348232DOI: 10.1016/j.ebiom.2018.03.019ISI: 000430303000033OAI: oai:DiVA.org:uu-348232DiVA, id: diva2:1196935
Funder
Swedish Research Council, 2015-02417Swedish Diabetes AssociationSwedish Child Diabetes FoundationEXODIAB - Excellence of Diabetes Research in Sweden2018-04-112018-04-112020-06-05Bibliographically approved