Master of Medicine, Peking Union Medical College (2005)
Doctor of Philosophy, Hanover School of Medicine (2010)
Edgar Engleman, Postdoctoral Faculty Sponsor
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.
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
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