Prof. Renxi Wang
Prof. Renxi Wang
Beijing Institute of Brain Disorders, Capital Medical University, China
Title: The role of Stch (Hspa13) in plasma cells and lupus mouse
The generation of large numbers of plasma cells (PCs) is a main factor in systemic lupus erythematosus (SLE). We hypothesize that Stch (Hspa13), a member of the heat shock protein family, plays a critical role in the control of PC differentiation. To test the hypothesis, we used lipopolysaccharide (LPS)-activated B cells and a newly established mouse line with a CD19cre-mediated, B cell–specific deletion of Hspa13: Hspa13 cKO mice. We found that Hspa13 mRNA was increased in PCs from atacicept-treated lupus-prone mice and in LPS-stimulated plasmablasts (PBs) and PCs. A critical finding was that PBs and PCs but not naïve B cells and germinal center (GC) B cells expressed high levels of Hspa13. In contrast, the Hspa13 cKO mice had a reduction in BPs, PCs, and antibodies induced in vitro by LPS and in vivo by sheep red blood cells (SRCs)- or 4-hydroxy-3-nitrophenylacetyl (NP)-immunization. Accordingly, the Hspa13 cKO mice had reduced class-switched and somatically hypermutated antibodies with defective affinity maturation. Our work also showed that Hspa13 interacts with proteins (e.g., Bcap31) in the endoplasmic reticulum (ER) to positively regulate protein transport from the ER to the cytosol. Importantly, Hspa13 mRNA was increased in B220+ cells from patients with multiple myeloma (MM) or SLE, whereas Hspa13 cKO led to reduced autoantibodies and proteinuria in both pristane-induced lupus and lupus-prone MRL/lpr mouse models. Collectively, our data suggest that Hspa13 is critical for PC development and may be a new target for eliminating pathologic PCs.
Dr. Renxi Wang is an immunologist, professor, and lab director in Laboratory of Neuroimmunology, Beijing Institute of Brain Disorders, Capital Medical University. Dr. Wang mainly studies lymphocyte differentiation and function, and potential therapeutic targets for immune-related diseases including Parkinson's Disease, Alzheimer's Disease, multiple sclerosis, type I diabetes, uveitis, systemic lupus erythematosus, multiple myeloma, sepsis, viral H7N9 infectious diseases, paraquat poisoning. Particular interest is on cytokine signaling that regulate lymphocyte development and cell-fate decisions. The ultimate goal is to develop targeted therapy for immune-related diseases. Dr. Wang has got six grants (RMB > 6.5 millions) funded by National Science and Technology Major Project, National Nature and Science Fund and Beijing Natural Science Foundation. The Dr. Wang group has published more than 70 important scientific articles (Nat Med, Nat Commun, Cancer Res, Crit Care Med, Cell Mol Immunol, Mol Ther) with more than 380 impact factors and 2200 citations (h-index: 27). Dr. Wang serves as a supervisor and has instructed 2 postdoctoral fellow, 7 Ph.D. and 5 masters. Dr. Wang is an editorial board member for several scientific journals. He also serves as a reviewer for funding agencies including Chinese National Nature and Science Funds, the Beijing Natural Science Foundation and Czech Science Foundation and scientific journals such as Cell Mol Immunol, J Cell Mol Med, Oncotarget, Mol Immunol.