title: The signaling role of CD40 ligand in platelet biology and in platelet component transfusion.
abstract: The CD40 ligand (CD40L) is a transmembrane molecule of crucial interest in cell signaling in innate and adaptive immunity. It is expressed by a variety of cells, but mainly by activated T-lymphocytes and platelets. CD40L may be cleaved into a soluble form (sCD40L) that has a cytokine-like activity. Both forms bind to several receptors, including CD40. This interaction is necessary for the antigen specific immune response. Furthermore, CD40L and sCD40L are involved in inflammation and a panoply of immune related and vascular pathologies. Soluble CD40L is primarily produced by platelets after activation, degranulation and cleavage, which may present a problem for transfusion. Soluble CD40L is involved in adverse transfusion events including transfusion related acute lung injury (TRALI). Although platelet storage designed for transfusion occurs in sterile conditions, platelets are activated and release sCD40L without known agonists. Recently, proteomic studies identified signaling pathways activated in platelet concentrates. Soluble CD40L is a good candidate for platelet activation in an auto-amplification loop. In this review, we describe the immunomodulatory role of CD40L in physiological and pathological conditions. We will focus on the main signaling pathways activated by CD40L after binding to its different receptors.
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. chaker.aloui@univ-st-etienne.fr.
authors.forename: Chaker
authors.initials: C
authors.lastname: Aloui
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. antoine.prigent@efs.sante.fr.
authors.forename: Antoine
authors.initials: A
authors.lastname: Prigent
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. caroline-sut@hotmail.fr.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sut
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. tariket.sofiane@hotmail.fr.
authors.forename: Sofiane
authors.initials: S
authors.lastname: Tariket
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France.
authors.forename: Hind
authors.initials: H
authors.lastname: Hamzeh-Cognasse
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. bruno.pozzetto@univ-st-etienne.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pozzetto
authors.affiliation: INSERMu1016, Institut Cochin, Departement "Infection, Immunity and Inflammation", Paris 75014, France. Yolande.richard@inserm.fr.
authors.forename: Yolande
authors.initials: Y
authors.lastname: Richard
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. fabrice.cognasse@univ-st-etienne.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Cognasse
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. sandrine.laradi@efs.sante.fr.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Laradi
authors.affiliation: Immunity of Mucosa and Pathogen Agents Group (GIMAP-EA3064), University of Lyon, Saint-Etienne 42023, France. ogarraud@ints.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Garraud
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D019013:CD40 Antigens / Q000235:genetics; D023201:CD40 Ligand / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D017713:Platelet Transfusion; D015398:Signal Transduction
chemical_list: D019013:CD40 Antigens; D023201:CD40 Ligand