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. PMCID: PMC4563689


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.


Hwang Y, Hsu H-C, Lim F, Wu Q, Yang P, Fisher G, Hunter GR and Mountz JD. 2013. Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging. Advances in Aging Research 2(2), 72-80. PMCID: PMC4226219


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) PMCID: PMC3979745


Li J, Yang PA, Wu Q, Li, H, Ding Y, Hsu H-C, Spalding DM, and Mountz JD. 2013. Death receptor 5-targeted depletion of interleukin 23 producing macrophages, Th1, and Th1/17 associated with defective tyrosine phosphatase in mice and patients with rheumatoid arthritis. Arthritis & Rheum 65(10), 2594-2605. (Supplementary Table). PMCID: PMC3993980


Ding Y, Li J, Wu Q, Yang P, Luo B, Xie S, Druey KM, Zajac AJ, Hsu H-C, and Mountz JD. 2013. IL-17RA is essential for optimal localization of follicular T helper cells in the germinal center light zone to promote autoantibody-producing B cells. J Immunol 191:1614-1624. PMCID: PMC3819396


Li J, Hsu HC, Yang P, Wu Q, Li H, Edgington LE, Bogyo M, Kimberly RP, Mountz JD. 2011. Treatment of arthritis by macrophage depletion and immunomodulation: Testing an apoptosis-mediated therapy in a humanized death receptor mouse model. Arthritis Rheum. 64(4): 1098-1109. PMID: 22006294 Supplementary Table 1 PMCID: PMC3596268


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.


Mountz JD, Li J, Hsu HC. Systemic autoimmunity caused by Fas deficiency in macrophages - a new perspective of the first identified autoimmune gene. Arthritis Rheum. 64(3): 609-612. PMID: 22139895


Hsu H-C, Zhou T, Kim H, Barnes S, Yang P-A, Wu Q, Zhou J, Freeman BA, Luo M and Mountz, JD.  2006. Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis.  Arthritis Rheum  54:343-355. PMID: 16385526


Hsu H-C, Scott DK, Zhang P, Yang P, Wu Q, Shroeder HW Jr, Gerald LB, Ravssin E, Jazwinski M and Mountz JD.  2006. CD8 T-cell immune phenotype of successful aging.  Mech Ageing Dev, 127:231-239. PMID: 16313945


Chen J, Wu Q, Yang P, Hsu H-C and Mountz JD. 2006.  In vivo analysis of adenovirus-specific cytotoxic T lymphocyte response in mice deficient in CD28, fas ligand, and perforin.  Hum Gene Ther 17:669-682. PMID: 16776575


Chen J, Wu Q, Yang P, Hsu H-C and Mountz JD. 2006.  Determination of specific CD4 and CD8 T cell epitopes after AAV2- and AAV8-hF.IX gene therapy.  Mol Ther 13:260-269. PMID: 16324888


Hsu H-C, Wu Y, Yang P, Wu Q, Fitzgerald A, Chen J, Job G, Wang J, Accatitti-Loper MA, Grizzle WE, Carter RH and Mountz JD.  2007. Over-expression of AID in B cells is associated with production of highly pathogenic autoantibodies.  J Immunol 178:5357-5365.  PMID: 17404321


Hsu H-C, Yang PA, Wu Q, Riley M, Wang J, Chen J, Tousson A, Stanus AA, Le TV, Xu H, Lorenz RG, Kolls J, Carter RH, Chaplin D, Lu L, Williams RW and Mountz JD. 2008. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice.  Nature Immunol 9:166-175. PMID: 18157131


Wang, J, Li J, Wu Q, Yang PA, Pawar RD, Xie S, Timares L, Raman C, Chaplin DD, Lu L, Mountz JD, and Hsu H-C.  2010. Marginal Zone Precursor B Cells as Cellular Agents for Type I IFN Promoted Antigen Transport in Autoimmunity.  Journal Immunol, 184: 442-451. PMID: 19949066


Xie S, Hsu H-C, Wang J, Wu Q, Li H, Li J, and Mountz JD. 2010 IL-17 activates the classical NF-kB signaling pathway to upregulate chemokine signal inhibitor molecules RGS16 and RGS13 in autoimmune B cells of BXD2 mice.  J. Immunol., 184: 2289-2296.PMID: 20139273


Chen J, Li J, Lim FC, Wu Q, Douek DC, Scott DK, Ravussin E, Hsu H-C, Jazwinski SM, Mountz JD 2010. for The Louisiana Healthy Aging Study. Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3. Mech Ageing Dev, 131:29-37 PMID: 19941883


Hsu HC, Mountz JD. 2010 Metabolic syndrome, hormones, and maintenance of T cells during aging. Curr Opin Immunol. 22(4): 541-548 PMID: 20591642


Jazwinski SM, Kim S, Dai J, Li L, Bi X, Jiang JC, Arnold J, Batzer MA, Walker JA, Welsh DA, Lefante CM, Volaufova J, Myers L, Su LJ, Hausman DB, Miceli MV, Ravussin E, Poon LW, Cherry KE, Welsch MA; Georgia Centenarian Study and the Louisiana Healthy Aging Study. HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging. Aging Cell. 9(5):698-708. PMID: 20569235


Hsu H-C, Yang PA, Wu Q, Wang J, Godwin J, Guentert T, Li J, Stockard CR, Le T, Chaplin DD, Grizzle WE, and Mountz, JD. 2011. Inhibition of the catalytic function of activation-induced cytidine deaminase (AICDA) promotes apoptosis of germinal center B cells. Arthritis Rheum, 63(7): 2038 - 2048 PMID: 21305519 (Supplementary Table)


Wang JH, Wu Q, Yang PA, Li H, Li J, Mountz JD and Hsu H-C.. 2011. Type I IFN-dependent CD86high marginal zone-precursor B cells are potent T-cell costimulators. Arthritis Rheum, 63(4): 1054-1064 PMID: 21225691


Mountz, JD, Wang JH, Xie S and Hsu H-C. 2011. Cytokine regulation of B-cell migratory behavior favors formation of germinal centers in autoimmune disease. Discovery Medicine 11(56):76-85. PMID: 21276413

 

SOM Epilogue Menu