AUTHOR=Ponomarev Eugene D. TITLE=Fresh Evidence for Platelets as Neuronal and Innate Immune Cells: Their Role in the Activation, Differentiation, and Deactivation of Th1, Th17, and Tregs during Tissue Inflammation JOURNAL=Frontiers in Immunology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.00406 DOI=10.3389/fimmu.2018.00406 ISSN=1664-3224 ABSTRACT=

Recent studies suggest that in addition to their common function in the regulation of thrombosis and hemostasis, platelets also contribute to tissue inflammation affecting adaptive immunity. Platelets have a number of pro-inflammatory and regulatory mediators stored in their α-granules and dense granules, which are promptly released at sites of inflammation or tissue injury. Platelet-derived mediators include cytokines (IL-1α, IL-1β, and TGFβ1), chemokines (CXCL4 and CCL3), immunomodulatory neurotransmitters (serotonin, dopamine, epinephrine, histamine, and GABA), and other low-molecular-weight mediators. In addition, activated platelets synthesize a number of lipid pro-inflammatory mediators such as platelet-activating factor and prostaglandins/thromboxanes. Notably, platelets express multiple toll-like receptors and MHC class I on their surface and store IgG in their α-granules. Platelet-derived factors are highly effective in directly or indirectly modulating the priming and effector function of various subsets of T cells. Besides secreting soluble factors, activated platelets upregulate a number of integrins, adhesion molecules, and lectins, leading to the formation of platelet–T cells aggregates. Activated platelets are able to instantly release neurotransmitters acting similar to neuronal presynaptic terminals, affecting CD4 T cells and other cells in close contact with them. The formation of platelet–T cell aggregates modulates the functions of T cells via direct cell–cell contact interactions and the local release of soluble factors including neurotransmitters. New data suggest an important role for platelets as neuronal and innate-like cells that directly recognize damage- or pathogen- associated molecular patterns and instantly communicate with T cells.