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=Volume 9 - 2018

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 alpha- and dense granules, which are promptly released at sites of inflammation or tissue injury. Platelet-derived mediators include cytokines (IL-1α, IL-1β, TGFβ1), chemokines (CXCL4, CCL3), immunomodulatory neurotransmitters (serotonin, dopamine, epinephrine, histamine, GABA) and other low molecular weight mediators. In addition, activated platelets synthesize a number of lipid pro-inflammatory mediators such as platelets-activating factor, and prostaglandins/thromboxanes. Notably, platelets express multiple TLRs and MHC class I on their surface and store IgG in their α-granules. Platelet-derived factors are highly effective at 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 pre-synaptic 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.