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PDGF upregulates CLEC-2 to induce T regulatory cells

Sudhanshu Agrawal1, Sreerupa Ganguly1, Pega Hajian1

  • 1Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.

Oncotarget
|September 30, 2015
PubMed

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.

Keywords:
Clec-2Immune responseImmunityImmunology and Microbiology SectionPDGFT regulatory cellsdendritic cellplateletspodoplanin

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