title: Platelet-derived RANK ligand enhances CCL17 secretion from dendritic cells mediated by thymic stromal lymphopoietin.
abstract: Dendritic cells (DCs) play an integral role in cellular cascade that initiate and maintain Th2 responses in allergy. In this study, we examined the interaction between platelets and DCs to determine the role of platelets in the intervention of immune responses through modulation of DC functions. Blood-purified myeloid DCs, which had been stimulated with thymic stromal lymphopoietin (TSLP-DCs), formed aggregates with activated platelets. TSLP-DC maturation was induced after the interaction with TRAP6-activated platelets as indicated by an increase in the expression of CD86, CD40, and CD83. In addition, production of a Th2 cell-attracting chemokine, CCL17, was clearly upregulated by coculture of TSLP-DCs with TRAP6-activated platelets. We further found that an expression of RANK ligand (RANKL) on platelets was upregulated by the TRAP6 activation, and that, using the neutralizing antibody against RANKL, the platelet-derived RANKL induces the activation of TSLP-DCs. Thus, activated platelets can intervene in adaptive immune responses through induction of functional modulation of TSLP-DCs. Platelets have the ability to enhance the DC-mediated Th2 response and may contribute to the allergic inflammation. In conclusion, our study provides new insights in platelet functions and the possible mechanism of allergic responses that stem from DCs.
authors.affiliation: First Department of Internal Medicine, Kansai Medical University , Osaka , Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Nakanishi
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Noriko
authors.initials: N
authors.lastname: Inagaki-Katashiba
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.forename: Phan Thi Xuan
authors.initials: PT
authors.lastname: Vien
authors.forename: Kayoko
authors.initials: K
authors.lastname: Kibata
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.forename: Shosaku
authors.initials: S
authors.lastname: Nomura
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002448:Cell Adhesion; D054414:Chemokine CCL17 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation; D010974:Platelet Aggregation; D053245:RANK Ligand / Q000378:metabolism* / Q000494:pharmacology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000954:Antigens, Surface; D054414:Chemokine CCL17; D016207:Cytokines; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D000094632:Thymic Stromal Lymphopoietin
keywords: CCL17; RANK ligand; dendritic cells; platelets; thymic stromal lymphopoietin