Hsu 2017Associate Professor of Medicine

Address:

Shelby Building, Room 311
1825 University Boulevard
35294-2182

 

Telephone:(205) 934-8909
Fax: 205-975-6648
Email: rheu078@uab.edu

Dr. Hsu's webpage in the School of Medicine

 

Education

BS, Chinese Culture University, Taipei, Taiwan, 1986
MS, Rutgers University, New Brunswick, NJ, 1990
PhD, Rutgers University, New Brunswick, NJ, 1995
Postdoctoral Fellow, University of Alabama at Birmingham, 1999

 

Research Description

We have identified that autoimmune BXD2 mice exhibit unique features, including spontaneous formation of germinal centers, increased expression of activation-induced cytidine deaminase (AID), increased production of pathogenic autoantibodies that are polyreactive, significantly increased percentage of IL-17high CD4 TH cells (TH-17) and IL-17Rhigh B cells, and significantly increased numbers of type I interferon producing plasmacytoid dendritic cells in the spleens of these mice. We are currently studying the inter-connection of high IL-17, high type I IFN and the development of autoreactive B cells related to B-cell tolerance loss at the transitional stage and the germinal center stage in BXD2 mice.

We currently study the close interaction between spleen marginal zone (MZ) B cells and MZ macrophages, and the implication of disrupting this close interaction in disease relapse following B-cell depletion therapy (BCDT) in systemic lupus erythematosus (SLE). In healthy individuals, the MZ B cells provide essential signals to maintain MZM survival and tolerogenic signaling to apoptotic debris derived autoantigens (AC-Ags) in the spleen MZ barrier. In SLE, a deficiency of tolerogenic MZMs occurs which disrupts the barrier and promotes an immunogenic environment including accumulation of uncleared AC-Ags and production of type I IFNs. Based on these results, we propose that BCDT in lupus, through depletion of the MZ B cells leads to a secondary depletion of the MZMs which may enable immunogenic responses to ACs in certain SLE patients. During deep B-cell depletion, when there are minimal B cells, this effect is not apparent. However, as B-cell repopulation occurs, the B cells are immediately subject to the immunogenic MZ microenvironment resulting in formation of autoreactive B cells and disease flares. We are currently developing strategies to overcome the loss of tolerogenic MZM barrier following BCDT with an ultimate goal to re-set B-cell tolerogenic state to achieve long-term remission. This work is currently supported by the Lupus Research Institute. http://lupusresearchinstitute.org/lupus-research/grant-recipients/hsu/hui-chen

 

Publications

Click here for a more complete list of publications on PubMed. Below are a few selected papers.


Li H, Fu Y-X, Wu Q, Zhou Y, Crossman DK, Yang PA, Li J, Luo B, Morel LM, Kabarowski JH, Yagita H, Ware C, Hsu H-C, Mountz JD. 2015. Interferon-induced Defective Mechanosensing Signaling in Lupus Spleen Marginal Zone Macrophages. J Clin Invest. 125(7):2877-90. PMC4563689


Hamilton JA, Li J, Wu Q, Yang PA, Luo B, Li H, Bradley JE, Taylor JE, Randall TD, Mountz JD, and Hsu H-C. 2015. General Approach for Tetramer Based Identification of Autoantigen Reactive B Cells: Characterization of La and snRNP Reactive B Cells in Autoimmune BXD2 Mice. J Immunol, 194(10):5022-34. PMC4417409


Li H, Hsu H-C, Wu Q, Yang PA, Li J, Luo B, Cua D, Oukka M, Steele III CH, Grizzle, WE, and Mountz JD. 2014.  IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORγt. Nat Commun. 5:4259.  PMC4136447


Li H, Wu Q, Li J, Yang P, Zhu Z, Luo B, Hsu H-C, and Mountz JD. 2013. Cutting Edge: Defective follicular exclusion of apoptotic antigens due to marginal zone macrophage defects in autoimmune BXD2 mice. J Immunol 190(9):4465-9. PMC3656168.


Wang JH, New JS, Xie S, Yang PA, Wu Q, Li J, Luo B, Ding Y, Druey KM, Hsu H-C, and Mountz JD. 2013. Extension of the germinal center stage of B-cell development promotes autoantibodies in BXD2 mice. Arthritis & Rheum 65(10), 2703-2712. (Supplementary Table) PMC3979745

 

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