Agrawal Sudhanshu, Ganguly Sreerupa, Hajian Pega, Cao Jia-Ning, Agrawal Anshu
Division of Basic and Clinical Immunology, Department of Medicine, University of California, Irvine, CA, USA.
Oncotarget. 2015 Oct 6;6(30):28621-32. doi: 10.18632/oncotarget.5765.
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.
血小板衍生生长因子（PDGF）对免疫细胞的作用尚未阐明。在此，我们证明PDGF抑制人树突状细胞（DCs）的成熟并诱导白细胞介素-10（IL-10）分泌。将PDGF-DCs与T细胞共培养可诱导T细胞向分泌IL-10的、表达叉头框P3（FoxP3）的调节性T细胞极化。基因表达研究表明，PDGF可诱导DCs上C型凝集素样受体成员2（CLEC-2）受体的表达。此外，在DC-T细胞共培养中，转染了CLEC-2的DCs可诱导调节性T细胞产生。CLEC-2在血小板上天然表达。因此，为了确认CLEC-2是否负责诱导调节性T细胞，将T细胞与表达CLEC-2的血小板或可溶性CLEC-2一起培养。两种情况均导致调节性T细胞的诱导。调节性T细胞的产生可能是由于CLEC-2与其在T细胞上的配体血小板凝集素结合所致，因为血小板凝集素在T细胞上的交联也导致调节性T细胞的诱导。这些数据表明，PDGF上调细胞上CLEC-2的表达以诱导调节性T细胞。
