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PDGF upregulates CLEC-2 to induce T regulatory cells

Authors: Agrawal, Sudhanshu; Ganguly, Sreerupa; Hajian, Pega; Cao, Jia-Ning; Agrawal, Anshu;

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.

Country
United States
Keywords

Blood Platelets, dendritic cell, Cells, T-Lymphocytes, T regulatory cells, Immunology, Oncology and Carcinogenesis, 610, Transfection, T-Lymphocytes, Regulatory, Dose-Response Relationship, Lectins, Paracrine Communication, 2.1 Biological and endogenous factors, Clec-2, Humans, Lectins, C-Type, Immune response, Cells, Cultured, Platelet-Derived Growth Factor, Cultured, Membrane Glycoproteins, Biomedical and Clinical Sciences, C-Type, Dose-Response Relationship, Drug, Inflammatory and immune system, Immunity, Oncology and carcinogenesis, Forkhead Transcription Factors, Dendritic Cells, PDGF, Regulatory, Coculture Techniques, Interleukin-10, Up-Regulation, podoplanin, Phenotype, platelets, Immunology and Microbiology Section, Drug, Signal Transduction

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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
45
Top 10%
Top 10%
Top 10%
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gold