title: PDGF upregulates CLEC-2 to induce T regulatory cells.
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.
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Sreerupa
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Pega
authors.initials: P
authors.lastname: Hajian
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Cao
authors.affiliation: Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Anshu
authors.initials: A
authors.lastname: Agrawal
mesh_terms: D001792:Blood Platelets / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects*; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D000098853:Podoplanin
chemical_list: D051858:Forkhead Transcription Factors; D016753:Interleukin-10; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; C104778:CLEC2B protein, human; C418974:FOXP3 protein, human; C508609:IL10 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin; C095477:platelet-derived growth factor AB
keywords: Clec-2; Immune response; Immunity; Immunology and Microbiology Section; PDGF; T regulatory cells; dendritic cell; platelets; podoplanin