Bio

Professional Education


  • Master of Medicine, Peking Union Medical College (2005)
  • Doctor of Philosophy, Hanover School of Medicine (2010)

Stanford Advisors


Patents


  • Xiangyue Zhang. "China P.Rep. Patent China CN1824677 Alternatively spliced isoforms of human interleukin-23 receptor gene and application", Xiangyue Zhang and Li Liu, Peking Union Medical College and Chinese Academy of Medical Sciences, Aug 30, 2006

Research & Scholarship

Current Research and Scholarly Interests


Immune suppression; Immune tolerance; Dendritic cells; Regulatory myeloid cells; T cell immune responses; GVHD; Transplantation; Autoimmune diseases.

1) Understand the plasticity of myeloid cells and T cells in different immune-related diseases, like inflammation, cancer, autoimmune diseases, etc.
2) Understand how immune suppression and immune tolerance are formed in both physiological and pathological settings.
3) To apply the discoveries from the bench to the bedside.

Myeloid cells including DCs, macrophages and MDSCs are my foci, especially their function on different T cell lineage (Th1, Th2, Th17, Treg), or vice versa.

In collaboration with Prof. Samuel Strober, I am also working on a project to understand the role of DCs in the induction of immune tolerance to organ and bone marrow transplants.

Publications

All Publications


  • A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. Proceedings of the National Academy of Sciences of the United States of America Zhang, H., Gregorio, J. D., Iwahori, T., Zhang, X., Choi, O., Tolentino, L. L., Prestwood, T., Carmi, Y., Engleman, E. G. 2017

    Abstract

    Plasmacytoid dendritic cells (pDCs) are known mainly for their secretion of type I IFN upon viral encounter. We describe a CD2(hi)CD5(+)CD81(+) pDC subset, distinguished by prominent dendrites and a mature phenotype, in human blood, bone marrow, and tonsil, which can be generated from CD34(+) progenitors. These CD2(hi)CD5(+)CD81(+) cells express classical pDC markers, as well as the toll-like receptors that enable conventional pDCs to respond to viral infection. However, their gene expression profile is distinct, and they produce little or no type I IFN upon stimulation with CpG oligonucleotides, likely due to their diminished expression of IFN regulatory factor 7. A similar population of CD5(+)CD81(+) pDCs is present in mice and also does not produce type I IFN after CpG stimulation. In contrast to conventional CD5(-)CD81(-) pDCs, human CD5(+)CD81(+) pDCs are potent stimulators of B-cell activation and antibody production and strong inducers of T-cell proliferation and Treg formation. These findings reveal the presence of a discrete pDC population that does not produce type I IFN and yet mediates important immune functions previously attributed to all pDCs.

    View details for DOI 10.1073/pnas.1610630114

    View details for PubMedID 28167780

  • Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts. BLOOD: blood-2016-07-723015 Hongo, D., Tang, X., Zhang, X., Engleman, E. G., Strober, S. 2017
  • Akt and SHP-1 are DC-intrinsic checkpoints for tumor immunity. JCI insight Carmi, Y., Prestwood, T. R., Spitzer, M. H., Linde, I. L., Chabon, J., Reticker-Flynn, N. E., Bhattacharya, N., Zhang, H., Zhang, X., Basto, P. A., Burt, B. M., Alonso, M. N., Engleman, E. G. 2016; 1 (18)

    Abstract

    BM-derived DC (BMDC) are powerful antigen-presenting cells. When loaded with immune complexes (IC), consisting of tumor antigens bound to antitumor antibody, BMDC induce powerful antitumor immunity in mice. However, attempts to employ this strategy clinically with either tumor-associated DC (TADC) or monocyte-derived DC (MoDC) have been disappointing. To investigate the basis for this phenomenon, we compared the response of BMDC, TADC, and MoDC to tumor IgG-IC. Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells. In contrast, TADC and, surprisingly, MoDC remained inert upon contact with IC due to dysfunctional signaling following engagement of Fcγ receptors. Such dysfunction is associated with elevated levels of the Src homology region 2 domain-containing phosphatase-1 (SHP-1) and phosphatases regulating Akt activation. Indeed, concomitant inhibition of both SHP-1 and phosphatases that regulate Akt activation conferred upon TADC and MoDC the capacity to take up and process IC and induce antitumor immunity in vivo. This work identifies the molecular checkpoints that govern activation of MoDC and TADC and their capacity to elicit T cell immunity.

    View details for PubMedID 27812544

  • CCR7 is dispensable for the development and function of murine NK cells. (In revision) The Journal of Leukocyte Biology Yu, S., Moschovakis, G., Mishra, P., Zhang, X., Kremmer, E., Forster, R. 2016
  • Neonatal lymph node stromal cells drive myelodendritic lineage cells into a distinct population of CX3CR1+CD11b+F4/80+ regulatory macrophages in mice. Blood Zhang, X., Yu, S., Hoffmann, K., Yu, K., Förster, R. 2012; 119 (17): 3975-3986

    Abstract

    Beyond providing a scaffold for immune cells, recent studies indicate that lymph node stromal cells provide potent regulatory capacities that affect the quality of adaptive immune responses. In this study, we provide evidence that neonatal lymph node stromal cells (nnLNSCs) consistently promote the differentiation of macrophage dendritic cell progenitors as well as mature and immature dendritic cells into a distinct population of CX3CR1(+) CD11b(+)F4/80(+) regulatory macrophages (regM?). These cells possess remarkably low levels of T cell costimulatory molecules as well as MHC class II molecules. regM? do not interfere with early T-cell activation but, via nitric oxide secretion, efficiently suppress T-cell proliferation. Furthermore, CD4(+) T cells proliferating in the presence of regM? gain immunosuppressive capacity and M? isolated from day 3 nnLNs are T-cell immunosuppressive. Adoptive transfer of antigen-loaded regM? induce a profound antigen-specific immune suppression in vivo. Together our data show that nnLNSCs skew the differentiation of dendritic cells and their progenitors toward regM?, thus revealing a novel mechanism for local immune regulation.

    View details for DOI 10.1182/blood-2011-06-359315

    View details for PubMedID 22403256

  • Identification and expression analysis of alternatively spliced isoforms of human interleukin-23 receptor gene in normal lymphoid cells and selected tumor cells IMMUNOGENETICS Zhang, X. Y., Zhang, H. J., Zhang, Y., Fu, Y. J., He, J., Zhu, L. P., Wang, S. H., Liu, L. 2006; 57 (12): 934-943

    Abstract

    Interleukin 23 (IL-23) is a new member of the IL-12 family that plays a critical role in promoting the proliferation of memory T helper 1 cells. The heterodimerized IL-23 receptor is composed of a shared IL-12 receptor beta 1 (IL-12Rbeta1) and an IL-12Rbeta2-related molecule called IL-23R. The standard form of IL-23R is encoded by at least 12 exons. Here, we demonstrate that at least six spliced isoforms of IL-23R (IL-23R1 to 6) can be generated through alternative splicing. The splicing strategies for the IL-23R gene are complicated and most often result in the deletion of exon 7 and/or exon 10. Translation prediction revealed that these spliced variants result in either premature termination to give rise to a diverse form of receptor ectodomain, or a frameshift to generate various lengths of the IL-23R endodomain. Differential expressions of IL-23R spliced variants are observed in natural killer and CD3+ CD4+ T cells. The expressions of these spliced variants are also prevalently and complicatedly regulated in tumor cell lines. Interestingly, only IL-23R2 and/or IL-23R4 variants are predominantly detected in certain human lung carcinomas, but not in their resected normal margin tissues. Thus, our results indicate that the regulation of alternative splicing on the IL-23R gene is complicated, and the preferential expression of certain IL-23R spliced variants may be a contributive factor to the pathogenesis of certain cancers.

    View details for DOI 10.1007/s00251-005-0067-0

    View details for Web of Science ID 000235127600005

    View details for PubMedID 16372191

  • Cancer Immunosurveillance or not? (New View) Progress in Biochemistry and Biophysics Xiangyue Zhang, Zhiguang Li, Zhihai Qin 2005; 32 (11): 1093-1098
  • Progress in the study of IL-23 and IL-23 receptor. Basic Medical Sciences and Clinics Xiangyue Zhang, Shuhui Wang 2004; 24 (4): 457-461