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.

• CCL17
• dendritic cells
• platelets
• RANK ligand
• thymic stromal lymphopoietin

Acknowledgements

The authors thank Mr. Hiroyuki Gonda, Central Research of Laboratory, for his help in the flowcytometrical analyses.

Declaration of interest

The authors report no declarations of interest. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant numbers 21591289, 24591472, and 23590694).