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Faculty Detail    
Name HUI-CHEN HSU
  
Campus Address SHEL 311 Zip 2182
Phone  (205) 934-8909
E-mail  rheu078@uab.edu
Other websites http://www.uab.edu/medicine/rheumatology/faculty/33-area-2/primary-faculty/39-hui-chen-hsu-phd
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Med - Immunology/Rheumatology  Med - Immunology/Rheumatology Associate Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Associate Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Associate Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Associate Professor
Center  UAB Immunology Institute  UAB Immunology Institute Associate Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Immunology 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Education Chinese Culture University, Taipei, Taiwan BS 1986 Food Science and Nutrition Rutgers University, New Brunswick, NJ MS 1990 Nutritional Sciences Rutgers University, New Brunswick, NJ PhD 1995 Nutritional Sciences HONORS AND AWARDS 1992 , Clinical Immunology Society Science Recognition Award for New Investigator in the 7th Annual Conference of Clinical Immunology; 1992, First Place for Excellence in Inflammation Research in C. Gordon Van Armon Award competition in the 6th International Inflammation Research Association Conference, 1992, Gina Finzi Memorial Student Summer Fellowship; Lupus Foundation of America, Inc; 1992, Second Prize Award for Excellence in Research in the Department of Medicine Annual Poster Symposium, UMDNJ-Robert Wood Johnson Medical School; 1993, Student Travel Award at the National Meeting of the American College of Rheumatology; 1994, Trainee Investigator Award for Excellence in Scientific Research in the National Meeting of American Federation of Clinical Research; 1995, Chapter Grant Recipient from Arthritis Foundation New Jersey Chapter; 1997, Post-postdoctoral Fellowship from Arthritis Foundation, 1999, Huang Foundation Trainee Award from American Association of Immunologists; 2001, Young Faculty Research Award from Southern Society for Clinical Investigation; 2003, First Place for UAB Center for Aging Scientific Program Abstract Competition: Biology of Aging Area.

Society Memberships
Organization Name Position Held Org Link
American Association of Immunologists     
 



Research/Clinical Interest
Title
The BXD2 autoimmune mouse model of lupus and erosive arthritis
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 interconnection of high IL-17, high type I IFN and the development of spontaneous germinal centers in these mice. We have identified that a small population of B cells, known as marginal zone precursor B cells (MZ-P) that can be located in either the marginal zone or inside the follicle, express high levels of interferon alpha receptor (IFNaR). We showed that, in BXD2 mice, type I IFNs strongly signaled through IFNaR on these MZ-P B cells more than any other mature B cell subpopulations, which up-regulated the co-stimulatory molecule CD86 and the activation molecular CD69, but interestingly, down-modulated the effects of another localization molecule known as sphingosine-1-phosphate (S1P). S1P has been described as playing a key role in anchoring B cells in the marginal zone. However, under the influence of IFNaR signaling, down-regulation of the effects of S1P enables displacement of the MZ-P B cell from the marginal zone to the germinal center. In addition, these MZ-P B cells can carry antigens that they acquire in the marginal zone, and deliver them to the germinal center. At the same time, the MZ-P B cells serve as excellent antigen-presenting B cells to CD4 T cells in the germinal center light zone, and can intensify a germinal center response. These mechanisms were verified using BXD2 mice that lacked either the IFNaR or lacked the CD86 co-stimulatory molecule. Further understanding of the novel mechanisms of up-regulation of type I IFN by pDCs around autoantibody-producing germinal centers, and the development and delivery of autoantigens by MZ-P B cells is being analyzed to develop novel therapies for treatment of systemic lupus erythematosus.

Selected Publications 
Publication PUBMEDID
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. Interferon-induced Defective Mechanosensing Signaling in Lupus Spleen Marginal Zone Macrophages. J Clin Investigation, In press.    
Hamilton JA, Li J, Wu Q, Yang PA, Luo B, Li H, Bradley JE, Taylor JE, Randall TD, Mountz JD, and Hsu H-C. 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, May 15;194(10):5022-34, 2015.   25888644  
Sang A, Zheng Y-Y, Yin Y, Dozmorov I, Li H, Hsu H-C, Mountz JD, and Morel L. Dysregulated cytokine production by dendritic cells modulates B cell responses in the NZM2410 mouse model of lupus. PLoS One. 9(8):e102151, 2014.  25093822  
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. IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORgt. Nat Commun. 5:4259, 2014.  25001511  
Ding Y, Li J, Yang P, Zajac A, Hsu H-C, Mountz JD. Interleukin-21 promotes germinal center reaction by skewing the follicular regulatory T cell to follicular helper T cell balance in autoimmune BXD2 mice. Arthritis Rheumatol. 66(9):2601-12, 2014.  24909430  
Li J, Yang PA, Wu Q, Li, H, Ding Y, Hsu H-C, and Mountz JD. Inhibition of terminal fucosylation reshapes human and mouse M1 macrophages and suppresses collagen II-induced arthritis. Arthritis Rheumatol. 66(9):2368-79, 2014.  24838610  
Ding Y, Li J, Wu Q, Yang P, Luo B, Xie S, Druey KM, Zajac AJ, Hsu H-C, and Mountz JD. 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, 2013.  23858031  
Li J, Yang PA, Wu Q, Li, H, Ding Y, Hsu H-C, Spalding DM, and Mountz JD. Death receptor 5-targeted depletion of interleukin-23-producing macrophages, Th17, and Th1/17 associated with defective tyrosine phosphatase in mice and patients with rheumatoid arthritis. Arthritis & Rheum 65(10), 2594-2605, 2013.  23818173  
Wang JH, New JS, Xie S, Yang PA, Wu Q, Li J, Luo B, Ding Y, Druey KM, Hsu H-C, and Mountz JD. Extension of the germinal center stage of B-cell development promotes autoantibodies in BXD2 mice. Arthritis & Rheum 65(10), 2703-2712, 2013.  23818250  
Mountz JD, Li J, Hsu HC. Systemic autoimmunity caused by fas deficiency in macrophages: a new perspective on the first identified autoimmunity gene. Arthritis Rheum. 64:609-12, 2012.  22139895 
Li J, Hsu HC, Yang P, Wu Q, Li H, Edgington LE, Bogyo M, Kimberly RP, Mountz JD. Treatment of arthritis by macrophage depletion and immunomodulation: testing an apoptosis-mediated therapy in a humanized death receptor mouse model. Arthritis Rheum 64:1098-109, 2012.
 		 22006294 
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. Inhibition of the catalytic function of activation-induced cytidine deaminase (AICDA) promotes apoptosis of germinal center B cells. Arthritis Rheum 63:2038-48, 2011.  21305519 
Mountz JD, Wang JH, Xie S, Hsu HC. Cytokine regulation of B-cell migratory behavior favors formation of germinal centers in autoimmune disease. Discov Med. 11:76-85, 2011.  21276413 
Wang JH, Wu Q, Yang PA, Li H, Li J, Mountz JD and Hsu H-C. Type I IFN-dependent CD86high Marginal Zone-Precursor B Cells are Potent T-Cell Costimulators. Arthritis Rheum 63:1054-64, 2011.  21225691 
Xie S, Hsu H-C, Wang J, Wu Q, Li H, Li J, d John D. Mountz. IL-17 activates the classical NF-kB signaling pathway to upregulate chemokine signal inhibitor molecules RGS16 in autoimmune B cells of BXD2 mice. The Journal of Immunology 184:2289-96, 2010.  20139273 
Wang JH, Li J, Wu Q, Yang P, Pawar RD, Xie S, Timares L, Raman C, Chaplin DD, Lu L, Mountz JD, Hsu HC. Marginal zone precursor B cells as cellular agents for Type I IFN-promoted antigen transport in autoimmunity. The Journal of Immunology 184:442-451, 2010.   19949066  
Xu X, Hsu H-C, Grizzle WE, Chatham WW, Wu Q, Stockard CR, Yang PA, Tunmire D, Holers M and Mountz JD. Increased expression of activation-induced cytidine deaminase (AID) is associated with anti-CCP and rheumatoid factor (RF) in rheumatoid arthritis (RA). Scan J Immunol 70:309-316, 2009.   19703021  
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. Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nature Immunol 9:166-175, 2008.   18157131 
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. Over-expression of AID in B cells is associated with production of highly pathogenic autoantibodies. J Immunol 178:5357-5365, 2007.   17404321 
Hsu H-C, Zhou T, Kim H, Barnes S, Yang P-A, Wu Q, Zhou J, Freeman BA, Luo M and Mountz, JD. Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis. Arthritis Rheum 54:343-355, 2006.  16385526  
Mountz JD, Yang PA, Wu Q, Zhou J, Tousson A, Fitzgerald A, Allen J, Wang X, Cartner S, Grizzle WE, Yi N, Lu L, Williams RW and Hsu H-C. Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in BXD2 recombinant inbred strain of mice. Scan J Immunol 61:128-138, 2005.  15683449 
 

Keywords
BXD2, lupus, arthritis, IL-17, type I IFN, apoptotic cells