Wenhao Chen, M.D., Ph.D.
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Assistant Professor e-mail address: Wenhao.Chen@UToledo.edu office phone number: (419) 383-6673 fax number: (419) 383-3002 |
Recirculating T lymphocytes, recognizing their specific antigens on the surface of
antigen-presenting cells, exert most adaptive immune and
autoimmune responses. My research is focused on identifying the molecular mechanisms
that regulate activation, differentiation, apoptosis,
and tolerance in T lymphocytes. My current project aims at identification of "unique
cytokine milieu" required for the generation of
memory T (antigen-experienced T cells that persist long-term) vs CD4+CD25+Foxp3+ regulatory
T cells (maintaining self-tolerance and suppressing
various immune responses). The results of these studies will lead us to the development
of novel therapeutic strategies for preventing T
cell-mediated transplant rejection, autoimmune diseases (e.g., type 1 diabetes), and
other immune disorders.
Representative
publications:
Wang G, Khattar M, Guo Z, Miyahara Y, Linkes SP, Sun Z, He X, Stepkowski SM, Chen W. IL-2-deprivation and TGF-beta are two non-redundant suppressor mechanisms of
CD4(+)CD25(+) regulatory T cell which jointly restrain CD4(+)CD25(-) cell activation.
Immunol Lett. 132:61, 2010.
Guo Z, Wang G, Miyahara Y, Khattar
M, Linkes SP, Wang C, Xia J, Pan Y, Chen W, He X, Stepkowski SM. IL-7, but not thymic stromal lymphopoietin (TSLP), contributes to the
programmatic generation of memory CD4+ T cells. Immunol. Lett. 2010 128:116-123.
Wang G, Miyahara Y, Guo Z, Khattar M, Stepkowski SM, Chen W. "Default" generation of neonatal regulatory T cells. J Immunol. 2010 185:71-78 .
Khattar M, Chen W, Stepkowski SM Expanding and converting regulatory T cells: a horizon for immunotherapy. Arch Immunol Ther Exp (Warsz). 2009 May-June; 57(3):199-204.
Diao J, Winter E, Chen W, Xu F, Cattral MS. Antigen transmission by replicating antigen-bearing dendritic cells. J Immunol. 2007 Sep 1;179(5):2713-21.Chen W, Diao J, Stepkowski SM, Zhang L. Both infiltrating regulatory T cells and insufficient antigen presentation are involved in long-term cardiac xenograft survival. J Immunology 2007 Aug 1;179(3):1542-8.
Ford MS, Chen W, Wong S, Li C, Vanama R, Elford AR, Asa SL, Ohashi PS, Zhang L. Peptide-activated double-negative T cells can prevent autoimmune type-1 diabetes development. Eur J Immunol. 2007 Aug;37(8):2234-41.
Thomson CW, Mossoba ME, Siatskas C, Chen W, Sung A, Medin JA, Zhang L. Lentivirally transduced recipient-derived dendritic cells serve to ex vivo expand functional FcR-sufficient double negative regulatory T cells. Mol Ther. 2007 Apr;15(4):818-24.
Ford MS, Zhang ZX, Chen W, Zhang L. Double-negative T regulatory cells can develop outside the thymus and do not mature from CD8+ T cell precursors. J Immunol. 2006 Sep 1;177(5):2803-9.
Thomson CW, Teft WA, Chen W, Lee BP, Madrenas J, Zhang L. FcR gamma presence in TCR complex of double-negative T cells is critical for their regulatory function. J Immunol. 2006 Aug 15;177(4):2250-7.
Diao J, Winter E, Cantin C, Chen W, Kelvin D, Phillips J, Cattral MS. In situ replication of immediate dendritic cell (DC) precursors contributes to conventional DC homeostasis in lymphoid tissue. J Immunol. 2006 Jun 15;176(12):7196-206.
Lee BP, Chen W, Shi H, Der S, Forster R, Zhang L. CXCR5/CXCL13 interaction is important for double negative T cell homing to cardiac allografts. J Immunol. 2006 May 1; 176(9):5276-83.
Chen W, Zhou D, Torrealba JR, Waddell TK, Grant D, Zhang L. Donor lymphocyte infusion induces long-term donor-specific cardiac xenograft survival through activation of recipient double-negative regulatory T cells. J Immunol. 2005 Sep 1;175(5):3409-16.
Mendicino M, Liu M, Ghanekar A, He W, Koscik C, Shalev I, Javadi M, Turnbull J, Chen W, Fung L, Sakamoto S, Marsden P, Waddell TK, Phillips MJ, Gorczynski R, Levy GA, Grant D. Targeted deletion of Fgl-2/fibroleukin in the donor modulates immunologic response and acute vascular rejection in cardiac xenografts. Circulation. 2005 Jul 12;112(2):248-56.
Lee BP, Mansfield E, Hsieh SC, Hernandez-Boussard T, Chen W, Thomson CW, Ford MS, Bosinger SE, Der S, Zhang ZX, Zhang M, Kelvin DJ, Sarwal MM, Zhang L. Expression profiling of murine double-negative regulatory T cells suggest mechanisms for prolonged cardiac allograft survival. J Immunol. 2005 Apr 15;174(8):4535-44.
Chen W, Langer RM, Janczewska S, Furian L, Geary R, Qu X, Wang M, Verani R, Condon T, Stecker K, Bennett CF, Stepkowski SM. Methoxyethyl-modified intercellular adhesion molecule-1 antisense phosphorothiateoligonucleotides inhibit allograft rejection, ischemic-reperfusion injury, and cyclosporine-induced nephrotoxicity. Transplantation. 2005 Feb 27;79(4):401-8.
Diao J, Winter E, Chen W, Cantin C, Cattral MS. Characterization of distinct conventional and plasmacytoid dendritic cell-committed precursors in murine bone marrow. J Immunol. 2004 Aug 1;173(3):1826-33.
Chen W, Ford M, Young K, Cybulsky MI, Zhang L. Role of DN regulatory T cells in long-term cardiac xenograft survival. J Immunol. 2003 Feb 15;170(4):1846-53.
Stepkowski SM, Qu X, Wang M-E, Tian L, Chen W, Wancewicz EV, Johnston JF, Bennett CF, Monia BP. Inhibition of C-raf expression by antisense oligonucleotides extends heart allograft survival in rats. Transplantation. 2000 Aug 27;70(4):656-61.
Chen W, Bennett CF, Wang ME, Dragun D, Tian L, Stecker K, Clark JH, Kahan BD, Stepkowski SM. Perfusion of kidneys with unformulated "naked" intercellular adhesion molecule-1 antisense oligodeoxynucleotides prevents ischemic/reperfusion injury. Transplantation.1999 Sep 27;68(6):880-7.
Depre C, Shipley GL, Chen W, Han Q, Doenst T, Moore ML, Stepkowski S, Davies PJ, Taegtmeyer H. Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy. Nature Medicine. 1998 Nov;4(11):1269-75.
Stepkowski SM, Wang ME, Condon TP, Cheng-Flournoy S, Stecker K, Graham M, Qu X, Tian L, Chen W, Kahan BD, Bennett CF. Protection against allograft rejection with intercellular adhesion molecule-1 antisense oligodeoxynucletides. Transplantation. 1998 Sep 27; 66(6):699-707.
Invited Articles (Reviews, Editorials, etc.) in Journals and Books:
Chen W, Zhang L. Regulatory T cell subsets and their roles in transplantation tolerance. Curr Opin Organ Transplant. 2006 Aug; 11:373.
Ford MS, Chen W, Zhang L. The immunoregulatory properties of double negative T cells. Altered Immunoregulation and Human Disease. 2005: 115-135.
Chen W, Ford MS, Young KJ, Zhang L. The role and mechanisms of Double Negative regulatory T cells in the suppression of immune responses. Cellular & Molecular Immunology. 2004 Oct; 1(5): 328-335.
Chen W, Ford MS, Young KJ, Zhang L. Infusion of in vitro-generated DN T regulatory cells induces permanent cardiac allograft survival in mice. Transplant Proc. 2003 Nov;35(7):2479-80.
Stepkowski SM, Chen W, Geary R, Wang ME, Condon T, Stecker K, Bennett CF. An oral formulation for intracellular adhesion molecules-1 antisense oligonucleotides. Transplant Proc. 2001 Nov;33(7-8):3271.
Stepkowski SM, Chen W, Bennett CF, Condon TP, Stecker K, Tian L, Kahan BD. Phosphorothioate/methoxyethyl-modified ICAM-1 antisense oligonucleotides improves prevention of ischemic/reperfusion injury(1). Transplant Proc. 2001 Nov;33(7-8):3705-6.
Chen W, Bennet CF, Condon TP, Stecker K, Tian L, Kahan BD, Stepkowski SM. Methoxyethyl modification of phosphorothioate ICAM-1 antisense oligonucleotides improves prevention of ischemic/reperfusion injury. Transplant Proc. 2001 Feb-Mar; 33(1-2):854.
Stepkowski SM, Chen W, Geary R, Wang ME, Condon T, Stecker K, Bennett CF. Development of an oral formulation for ICAM-1 antisense oligonucletides. Transplant Proc. 2001 Feb-Mar; 33(1-2):38.