Research Papers: Immunology:

PDGF upregulates CLEC-2 to induce T regulatory cells

Sudhanshu Agrawal, Sreerupa Ganguly, Pega Hajian, Jia-Ning Cao and Anshu Agrawal _

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Oncotarget. 2015; 6:28621-28632. https://doi.org/10.18632/oncotarget.5765

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Sudhanshu Agrawal1, Sreerupa Ganguly1, Pega Hajian1, Jia-Ning Cao1 and Anshu Agrawal1

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


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.

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