PDGF upregulates CLEC-2 to induce T regulatory cells

Abstract

// Sudhanshu Agrawal 1 , Sreerupa Ganguly 1 , Pega Hajian 1 , Jia-Ning Cao 1 and Anshu Agrawal 1 1 Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA Correspondence to: Anshu Agrawal, email: // Keywords : Clec-2, dendritic cell, platelets, T regulatory cells, PDGF, podoplanin, Immunology and Microbiology Section, Immune response, Immunity Received : August 04, 2015 Accepted : September 12, 2015 Published : September 21, 2015 Abstract The effect of platelet derived growth factor (PDGF) on immune cells is not elucidated. Here, we demonstrate PDGF inhibited the maturation of human DCs and induced IL-10 secretion. Culture of PDGF-DCs with T cells induced the polarization of T cells towards FoxP3 expressing T regulatory cells that secreted IL-10. Gene expression studies revealed that PDGF induced the expression of C-type lectin like receptor member 2, (CLEC-2) receptor on DCs. Furthermore, DCs transfected with CLEC-2 induced T regulatory cells in DC-T cell co-culture. CLEC-2 is naturally expressed on platelets. Therefore, to confirm whether CLEC-2 is responsible for inducing the T regulatory cells, T cells were cultured with either CLEC-2 expressing platelets or soluble CLEC-2. Both conditions resulted in the induction of regulatory T cells. The generation of T regulatory cells was probably due to the binding of CLEC-2 with its ligand podoplanin on T cells, since crosslinking of podoplanin on the T cells also resulted in the induction of T regulatory cells. These data demonstrate that PDGF upregulates the expression of CLEC-2 on cells to induce T regulatory cells.