Dr. Yongguang Yang's Research
Humanized mouse models for the study of human immune function in vivo: We have developed a humanized mouse model, in which human T cells are generated in an autologous human thymus. These humanized mice show normal human thymopoiesis, systemic repopulation with multilineages of human lymphohematopoietic cells (e.g., T, B and dendritic cells), formation of secondary lymphoid organs with normal architecture, and strong antigen-specific T cell and antibody responses upon immunization. We are currently using this model as an in vivo model system for elucidating human immune responses in allogeneic and xenogeneic transplantation settings.
Inhibitory receptor-ligand interactions in xenograft rejection: CD47 is a ligand of an inhibitory receptor, SIRPα, and its interaction with SIRPα on macrophages prevents phagocytosis of autologous hematopoietic cells. We have discovered that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages. We also demonstrated that the phagocytic activity of macrophages against CD47-deficient cells is conferred by CD47 expression on nonhematopoietic cells, and that lack of CD47 on nonhematopoietic cells induces macrophage tolerance to CD47-deficient cells. Ongoing research is focused on defining the mechanisms of macrophage tolerance and developing novel strategies for controlling xenograft rejection by macrophages.
GVHD vs. GVL in allogeneic hematopoietic cell transplantation (allo-HCT): Graft-vs.-host disease (GVHD) remains the major complication of allo-HCT, the only curative therapy for many hematopoietic malignancies. We have shown that IFN-gamma plays an important role in controlling the alloresponses of donor T cells and determines whether they will predominantly mediate GVHD or graft-vs.-leukemia (GVL) effects. We are currently studying the molecular and cellular mechanisms by which IFN-gamma regulates the alloreactivity of donor T cells.
Hui Wang, MD, PhD
Jinxing Xia, PhD
Yanan Ding, MS
Mingyou Zhang, PhD
Satoshi Yoshihara, PhD
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- Yang Y, Wang H, Yu H, Yeap BY, Liang T, Wang G, Cheng T, Yang YG. IFN-gamma promotes graft-versus-leukemia effects without directly interacting with leukemia cells in mice after allogeneic hematopoietic cell transplantation. Blood (In press)
- Wang H, Wu X, Wang Y, Oldenborg PA, Yang YG. CD47 is required for suppression of allograft rejection by donor specific transfusion. J Immunol. 2010;184:3401-3407.
- Habiro K, Sykes M, Yang YG. Induction of human T cell tolerance to pig xenoantigens via thymus transplantation in mice with an established human immune system. American Journal of Transplantation 2009;9:1324-1429.
- Wang H, Asavaroengchai W, Yeap BY, Wang MG, Wang S, Sykes M, Yang YG. Paradoxical effects of IFN‑ in graft-vs.-host (GVH) disease reflect promotion of lymphohematopoietic GVH reactions and inhibition of epithelial tissue injury. Blood 2009;113:3612-3619.
- Tonomura N, Habiro K, Shimizu A, Sykes M, Yang YG. Antigen specific human T cell responses and T cell-dependent production of human antibodies in a humanized mouse model. Blood 2008;111:4293-4296.
- Yang YG, Sykes M. Xenotransplantation - Current Status and a Perspective on the Future. Nature Reviews Immunology 2007;7:519-531.
- Wang H, Madariaga ML, Wang S, Van Rooijen N, Oldenborg PA, Yang YG. Lack of CD47 on nonhematopoietic cells induces split macrophage tolerance to CD47null cells. Proc Natl Acad Sci USA 2007;104:13744-13749.
- Ide K, Wang H, Liu J, Wang X, Asahara T, Sykes M, Yang YG, Ohdan H. Role for CD47-SIRP signaling in xenograft rejection by macrophages. Proc Natl Acad Sci USA 2007;104(12):5062-5066.
- Wang H, VerHalen J, Madariaga ML, Xiang S, Wang S, Lan P, Oldenborg P-A, Sykes M, Yang YG. Attenuation of phagocytosis of xenogeneic cells by manipulating CD47. Blood 2007;109:836-842.
- Lan P, Tonomura N, Wang S, Yang YG. Reconstitution of a functional human immune system in immunodeficient mice through combined human fetal thymus/liver and CD34+ cell transplantation. Blood 2006;108:487–492.