PDGF upregulates CLEC-2 to induce T regulatory cells

被引:40
作者
Agrawal, Sudhanshu [1 ]
Ganguly, Sreerupa [1 ]
Hajian, Pega [1 ]
Cao, Jia-Ning [1 ]
Agrawal, Anshu [1 ]
机构
[1] Univ Calif Irvine, Dept Med, Div Basic & Clin Immunol, Irvine, CA 92717 USA
基金
美国国家卫生研究院;
关键词
Clec-2; dendritic cell; platelets; T regulatory cells; PDGF; podoplanin; Immunology and Microbiology Section; Immune response; Immunity; TOLEROGENIC DENDRITIC CELLS; LECTIN-LIKE RECEPTORS; PLATELET ACTIVATION; TH17; CELLS; PODOPLANIN; ANGIOGENESIS; MECHANISM; NETWORKS; CD4(+); GROWTH;
D O I
10.18632/oncotarget.5765
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:28621 / 28632
页数:12
相关论文
共 46 条
[1]   Dendritic cells control fibroblastic reticular network tension and lymph node expansion [J].
Acton, Sophie E. ;
Farrugia, Aaron J. ;
Astarita, Jillian L. ;
Mourao-Sa, Diego ;
Jenkins, Robert P. ;
Nye, Emma ;
Hooper, Steven ;
van Blijswijk, Janneke ;
Rogers, Neil C. ;
Snelgrove, Kathryn J. ;
Rosewell, Ian ;
Moita, Luis F. ;
Stamp, Gordon ;
Turley, Shannon J. ;
Sahai, Erik ;
Reis e Sousa, Caetano .
NATURE, 2014, 514 (7523) :498-+
[2]   Podoplanin-Rich Stromal Networks Induce Dendritic Cell Motility via Activation of the C-type Lectin Receptor CLEC-2 [J].
Acton, Sophie E. ;
Astarita, Jillian L. ;
Malhotra, Deepali ;
Lukacs-Kornek, Veronika ;
Franz, Bettina ;
Hess, Paul R. ;
Jakus, Zoltan ;
Kuligowski, Michael ;
Fletcher, Anne L. ;
Elpek, Kutlu G. ;
Bellemare-Pelletier, Angelique ;
Sceats, Lindsay ;
Reynoso, Erika D. ;
Gonzalez, Santiago F. ;
Graham, Daniel B. ;
Chang, Jonathan ;
Peters, Anneli ;
Woodruff, Matthew ;
Kim, Young-A. ;
Swat, Wojciech ;
Morita, Takashi ;
Kuchroo, Vijay ;
Carroll, Michael C. ;
Kahn, Mark L. ;
Wucherpfennig, Kai W. ;
Turley, Shannon J. .
IMMUNITY, 2012, 37 (02) :276-289
[3]   Altered innate immune functioning of dendritic cells in elderly humans: A role of phosphoinositide 3-kinase-signaling pathway [J].
Agrawal, Anshu ;
Agrawal, Sudhanshu ;
Cao, Jia-Ning ;
Su, Houfen ;
Osann, Kathryn ;
Gupta, Sudhir .
JOURNAL OF IMMUNOLOGY, 2007, 178 (11) :6912-6922
[4]   Increased IL-21 secretion by aged CD4+T cells is associated with prolonged STAT-4 activation and CMV seropositivity [J].
Agrawal, Anshu ;
Su, Houfen ;
Chen, Justine ;
Osann, Kathryn ;
Agrawal, Sudhanshu ;
Gupta, Sudhir .
AGING-US, 2012, 4 (09) :648-659
[5]   Human Dendritic Cells Activated via Dectin-1 Are Efficient at Priming Th17, Cytotoxic CD8 T and B Cell Responses [J].
Agrawal, Sudhanshu ;
Gupta, Sudhir ;
Agrawal, Anshu .
PLOS ONE, 2010, 5 (10)
[6]   The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture [J].
Astarita, Jillian L. ;
Cremasco, Viviana ;
Fu, Jianxin ;
Darnell, Max C. ;
Peck, James R. ;
Nieves-Bonilla, Janice M. ;
Song, Kai ;
Kondo, Yuji ;
Woodruff, Matthew C. ;
Gogineni, Alvin ;
Onder, Lucas ;
Ludewig, Burkhard ;
Weimer, Robby M. ;
Carroll, Michael C. ;
Mooney, David J. ;
Xia, Lijun ;
Turley, Shannon J. .
NATURE IMMUNOLOGY, 2015, 16 (01) :75-+
[7]   The platelet contribution to cancer progression [J].
Bambace, N. M. ;
Holmes, C. E. .
JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2011, 9 (02) :237-249
[8]   Mechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases [J].
Buckner, Jane Hoyt .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (12) :849-859
[9]   Transplantation tolerance and its outcome during infections and inflammation [J].
Chong, Anita S. ;
Alegre, Maria-Luisa .
IMMUNOLOGICAL REVIEWS, 2014, 258 (01) :80-101
[10]  
Colonna M, 2000, EUR J IMMUNOL, V30, P697