GABA exerts anti-inflammatory and immunosuppressive effects (P5175)

Gamma amino-butyric acid (GABA) is an inhibitory neurotransmitter in the CNS, but it also exerts important functions in the immune system and the islets of Langerhans. Thus, functional GABA receptors have been identified on immune cells and islet cells. Previously, we found that in both autoimmune (NOD) and streptozotocin (STZ)-induced diabetes GABA increases islet-cell mass, while exerting anti-apoptotic effects. GABA induced the regeneration of islet beta cells. It also suppressed inflammatory cytokine production, which is likely important in allowing survival of new islet beta cells. In this study, we examine how GABA exerts immunoprotective effects. We report that GABA suppresses both T cells and macrophages. It increases TGF-beta production and regulatory T cells (Tr or Treg). Notably, GABA inhibits NF-kB activation in both lymphocytes and pancreatic islet beta cells. It also protects beta cells from apoptosis induced by various mechanisms, and this may be related to NF-kB inhibition. The mechanisms by which GABA exerts these effects are largely unknown. However, in immune cells it stimulates GABA type A receptors, which act as ligand-gated chloride channels. This may open voltage-dependent calcium channels in the membrane and decrease intra-cellular calcium levels. Conclusion: GABA acts on both T cells and macrophages and exerts potent anti-inflammatory effects, which are protective in models of type 1 diabetes.