Positions

Overview

  • Dr. Hsu, Associate Professor of Medicine, studies the regulation of multiple types of immune cells in both humans and mice. Dr. Hsu has had a long history of interest and experience in studying mechanisms of autoimmune disease. She is the investigator who 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-17 producing CD4 T helper cells.

    Dr. Hsu has developed a two-tiered peptide microarray approach, coupled with epitope mapping of known autoantigens, to identify and characterize autoepitopes recognized by BXD2 autoreactive B cells. Using this method, tetramers were prepared from two linear peptides derived from two ribonucleic acid binding proteins (RBP): lupus La and 70 kDa U1 small nuclear ribonucleoprotein (snRNP). Dr. Hsu and colleagues have subsequently identified that there was reduction of transitional T1 B cells associated with a significantly higher frequency and greater numbers of RBP-reactive marginal zone precursor (MZ-P), transitional T3 and PDL-2+CD80+ memory B cells in BXD2 mice, compared to B6 mice.

    More recently, her collaboration with Drs Chatham and Mountz has led to a novel discovery that there was increased intracellular expression of IFN-β in B cells from a subset of African American SLE patients. She currently applies the 10x Chromium-based transcriptomics/BCR analysis to identify mechanisms leading to B-cell tolerance loss at different checkpoints in SLE.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2020 IL-23 promotes a coordinated B cell germinal center program for class-switch recombination to IgG2b in BXD2 miceJournal of Immunology.  205:346-358. 2020
    2019 Autoreactive B cells in SLE, villains or innocent bystanders?Immunological Reviews.  292:120-138. 2019
    2019 Dysregulation of T follicular helper cells in lupusJournal of Immunology.  202:1649-1658. 2019
    2018 Cutting edge: Intracellular IFN-β and distinct type i IFN expression patterns in circulating systemic lupus erythematosus B cellsJournal of Immunology.  201:2203-2208. 2018
    2018 Myeloid-derived suppressor cells impair B cell responses in lung cancer through IL-7 and STAT5Journal of Immunology.  201:278-295. 2018
    2018 Unmasking Fucosylation: from Cell Adhesion to Immune System Regulation and DiseasesCell Chemical Biology.  25:499-512. 2018
    2018 Role of production of type I interferons by B cells in the mechanisms and pathogenesis of systemic lupus erythematosusDiscovery medicine.  25:21-29. 2018
    2017 Cutting Edge: Endogenous IFN-β regulates survival and development of transitional B cellsJournal of Immunology.  199:2618-2623. 2017
    2016 Tamoxifen metabolite endoxifen interferes with the polyamine pathway in breast cancerAmino Acids.  48:2293-2302. 2016
    2015 General approach for tetramer-based identification of autoantigen-reactive B cells: Characterization of La- and snRNP-reactive B cells in autoimmune BXD2 miceJournal of Immunology.  194:5022-5034. 2015
    2015 Identification of follicular T helper cells in tissue sectionsMethods in Molecular Biology.  1291:13-25. 2015
    2015 Interferon-induced mechanosensing defects impede apoptotic cell clearance in lupusJournal of Clinical Investigation.  125:2877-2890. 2015
    2014 Dysregulated cytokine production by dendritic cells modulates B cell responses in the NZM2410 mouse model of lupusPLoS ONE.  9. 2014
    2014 IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORγtNature Communications.  5. 2014
    2014 Inhibition of fucosylation reshapes inflammatory macrophages and suppresses type II collagen-induced arthritisArthritis and Rheumatology.  66:2368-2379. 2014
    2014 Interleukin-21 promotes germinal center reaction by skewing the follicular regulatory T cell to follicular helper T cell balance in autoimmune BXD2 miceArthritis and Rheumatology.  66:2601-2612. 2014
    2013 The Dynamic Duo-Inflammatory M1 macrophages and Th17 cells in Rheumatic Diseases.Journal of Orthopedics & Rheumatology.  1:4. 2013
    2013 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 arthritisArthritis and Rheumatism.  65:2594-2605. 2013
    2013 Extension of the germinal center stage of B cell development promotes autoantibodies in BXD2 miceArthritis and Rheumatism.  65:2703-2712. 2013
    2013 IL-17RA is essential for optimal localization of follicular Th cells in the germinal center light zone to promote autoantibody-producing B cellsJournal of Immunology.  191:1614-1624. 2013
    2013 Cutting edge: Defective follicular exclusion of apoptotic antigens due to marginal zone macrophage defects in autoimmune BXD2 miceJournal of Immunology.  190:4465-4469. 2013
    2013 Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging.Advances in Aging Research.  2:72-80. 2013
    2012 Managing macrophages in rheumatoid arthritis by reform or removalCurrent Rheumatology Reports.  14:445-454. 2012
    2012 Systemic autoimmunity caused by fas deficiency in macrophages: A new perspective on the first identified autoimmunity geneArthritis and Rheumatism.  64:609-612. 2012
    2012 A potential estrogen mimetic effect of a bis(ethyl)polyamine analogue on estrogen receptor positive MCF-7 breast cancer cellsAmino Acids.  42:899-911. 2012
    2012 Treatment of arthritis by macrophage depletion and immunomodulation: testing an apoptosis-mediated therapy in a humanized death receptor mouse model.Arthritis and Rheumatism.  64:1098-1109. 2012
    2011 Longitudinal assessment of cognitive and psychosocial functioning after Hurricanes Katrina and Rita: Exploring disaster impact on middle-aged, older, and oldest-old adultsJournal of Applied Biobehavioral Research.  16:187-211. 2011
    2011 ReplyArthritis and Rheumatism.  63:3175-3177. 2011
    2011 Inhibition of the catalytic function of activation-induced cytidine deaminase promotes apoptosis of germinal center B cells in BXD2 miceArthritis and Rheumatism.  63:2038-2048. 2011
    2011 Type i interferon-dependent CD86high marginal zone precursor b cells are potent T cell costimulators in miceArthritis and Rheumatism.  63:1054-1064. 2011
    2011 Cytokine regulation of B-cell migratory behavior favors formation of germinal centers in autoimmune disease.Discovery medicine.  11:76-85. 2011
    2010 Metabolic syndrome, hormones, and maintenance of T cells during agingCurrent Opinion in Immunology.  22:541-548. 2010
    2010 IL-17 activates the canonical NF-κB signaling pathway in autoimmune B cells of BXD2 mice to upregulate the expression of regulators of G-protein signaling 16Journal of Immunology.  184:2289-2296. 2010
    2010 Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3Mechanisms of Ageing and Development.  131:29-37. 2010
    2010 Marginal zone precursor B cells as cellular agents for type I IFN-promoted antigen transport in autoimmunityJournal of Immunology.  184:442-451. 2010
    2010 Visualizing CD4 T-cell migration into inflamed skin and its inhibition by CCR4/CCR10 blockades using in vivo imaging modelBritish Journal of Dermatology.  162:487-496. 2010
    2009 Assessment of genetic shielding for adenovirus vectorsOpen Gene Therapy Journal.  2:1-11. 2009
    2009 Increased expression of activation-induced cytidine deaminase is associated with anti-CCP and rheumatoid factor in rheumatoid arthritisScandinavian Journal of Immunology.  70:309-316. 2009
    2008 Regulation of estrogenic effects by beclin 1 in breast cancer cellsCancer Research.  68:7855-7863. 2008
    2008 Optimization of capsid-incorporated antigens for a novel adenovirus vaccine approachVirology Journal.  5. 2008
    2008 Enhancement of cytotoxic T-lymphocyte response in aged mice by a novel treatment with recombinant AdIL-12 and wild-type adenovirus in rapid successionMolecular Therapy.  16:1500-1506. 2008
    2008 Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 miceNature Immunology.  9:166-175. 2008
    2007 Overexpression of activation-induced cytidine deaminase in B cells is associated with production of highly pathogenic autoantibodiesJournal of Immunology.  178:5357-5365. 2007
    2007 Quantitative trait locus (QTL) mapping in aging systemsMethods in Molecular Biology.  371:321-348. 2007
    2007 Quantitative trait locus (QTL) mapping in aging systems.Methods in Molecular Biology.  371:321-348. 2007
    2006 Principal component analysis of quantitative trait loci for immune response to adenovirus in miceHereditas.  143:189-197. 2006
    2006 Phenotype of genetically regulated thymic involution in young BXD RI strains of miceScandinavian Journal of Immunology.  64:287-294. 2006
    2006 In vivo analysis of adenovirus-specific cytotoxic T lymphocyte response in mice deficient in CD28, Fas ligand, and perforinHuman Gene Therapy.  17:669-682. 2006
    2006 CD8 T-cell immune phenotype of successful agingMechanisms of Ageing and Development.  127:231-239. 2006
    2006 Determination of specific CD4 and CD8 T cell epitopes after AAV2- and AAV8-hF.IX gene therapyMolecular Therapy.  13:260-269. 2006
    2006 Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritisArthritis and Rheumatism.  54:343-355. 2006
    2006 Tumor necrosis factor ligand-receptor superfamily and arthritis.Current Directions in Autoimmunity.  9:37-54. 2006
    2005 Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system functionNature Genetics.  37:233-242. 2005
    2005 Rheumatoid arthritis: safe and sound. 2005
    2005 Safe and sound 2005
    2005 Synovial fibroblasts promote osteoclast formation by RANKL in a novel model of spontaneous erosive arthritisArthritis and Rheumatism.  52:3257-3268. 2005
    2005 Primary adenovirus-specific cytotoxic T lymphocyte response occurs after viral clearance and liver enzyme elevation 2005
    2005 Genetic analysis of the antibody response to AAV2 and factor IXMolecular Therapy.  11:866-874. 2005
    2005 Impaired apoptosis and immune senescence - Cause or effect?Immunological Reviews.  205:130-146. 2005
    2005 Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in the BXD2 recombinant inbred strain of miceScandinavian Journal of Immunology.  61:128-138. 2005
    2005 Genetic regulation of thymic involutionMechanisms of Ageing and Development.  126:87-97. 2005
    2004 Nur77 family of nuclear hormone receptors 2004
    2004 Defective clearance of adenovirus in IRF-1-/- mice associated with defects in NK and T cells but not macrophagesScandinavian Journal of Immunology.  60:89-99. 2004
    2004 Regulation of apoptosis proteins in cancer cells by ubiquitinOncogene.  23:2009-2015. 2004
    2004 IL-12 Inhibits Thymic Involution by Enhancing IL-7- and IL-2-Induced Thymocyte ProliferationJournal of Immunology.  172:2909-2916. 2004
    2004 Novel Tumor Necrosis Factor α-Regulated Genes in Rheumatoid ArthritisArthritis and Rheumatism.  50:420-431. 2004
    2004 Identification of multiple genetic loci that regulate adenovirus gene therapy 2004
    2004 The Collaborative Cross, a community resource for the genetic analysis of complex traitsNature Genetics.  36:1133-1137. 2004
    2003 CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritisJournal of Clinical Investigation.  112:1332-1341. 2003
    2003 CII-DC-AdTRAIL cell gene therapy inhibits infiltration of CII-reactive T cells and CII-induced arthritis.Journal of Clinical Investigation.  112:1332-1341. 2003
    2003 The nature and identification of quantitative trait loci: A community's viewNature Reviews Genetics.  4:911-916. 2003
    2003 Age-related thymic involution in C57BL/6J x DBA/2J recombinant-inbred mice maps to mouse chromosomes 9 and 10Genes and Immunity.  4:402-410. 2003
    2003 Erratum: Cellular mechanism of thymic involution (Scandinavian Journal of Immunology (2003) 57 (410-422))Scandinavian Journal of Immunology.  58:118. 2003
    2003 Cellular mechanism of thymic involutionScandinavian Journal of Immunology.  57:410-422. 2003
    2003 Impact of immune senescence on human agingImmunology and Allergy Clinics of North America.  23. 2003
    2003 Origin of late-onset autoimmune diseaseImmunology and Allergy Clinics of North America.  23:65-82. 2003
    2002 Addition of six-His-tagged peptide to the C terminus of adeno-associated virus VP3 does not affect viral tropism or productionJournal of Virology.  76:12023-12031. 2002
    2002 Specific deletion of autoreactive T cells by adenovirus-transfected, Fas ligand-producing antigen-presenting cellsImmunologic Research.  26:235-246. 2002
    2002 BXD recombinant inbred mice represent a novel T cell-mediated immune response tumor modelInternational Journal of Cancer.  101:270-279. 2002
    2002 Different role of Apaf-1 in positive selection, negative selection and death by neglect in foetal thymic organ cultureScandinavian Journal of Immunology.  56:174-184. 2002
    2002 Hepatic DR5 induces apoptosis and limits adenovirus gene therapy product expression in the liverJournal of Virology.  76:5692-5700. 2002
    2002 Age-related change in thymic T-cell development is associated with genetic loci on mouse chromosomes 1, 3, and 11Mechanisms of Ageing and Development.  123:1145-1158. 2002
    2002 Beneficial influences of systemic cooperation and sociological behavior on longevityMechanisms of Ageing and Development.  123:963-973. 2002
    2002 Depletion of collagen II-reactive T cells and blocking of B cell activation prevents collagen II-induced arthritis in DBA/1j miceJournal of Immunology.  168:4164-4172. 2002
    2002 Molecular imaging: New applications for biochemistryJournal of Cellular Biochemistry.  162-171. 2002
    2002 Molecular imaging: new applications for biochemistry. 2002
    2002 Soluble Fas gene therapy protects against Fas-mediated apoptosis of hepatocytes but not the lethal effects of Fas-induced TNF-α production by Kupffer cellsCell Death and Differentiation.  9:626-635. 2002
    2001 Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticlesJournal of Immunological Methods.  256:89-105. 2001
    2001 Activated CD8+ T cells from aged mice exhibit decreased activation-induced cell deathMechanisms of Ageing and Development.  122:1663-1684. 2001
    2001 Defective Fas Ligand-Mediated Apoptosis Predisposes to Development of a Chronic Erosive Arthritis Subsequent to Mycoplasma pulmonis InfectionArthritis and Rheumatism.  44:2146-2159. 2001
    2001 Defective Fas ligand-mediated apoptosis predisposes to development of a chronic erosive arthritis subsequent to Mycoplasma pulmonis infection.Arthritis and Rheumatism.  44:2146-2159. 2001
    2001 Regulation of tumor necrosis factor α-mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase AktArthritis and Rheumatism.  44:1555-1567. 2001
    2001 Genetic dissection of age-related changes of immune function in miceScandinavian Journal of Immunology.  54:10-20. 2001
    2001 Regulation of tumor necrosis factor alpha-mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase Akt.Arthritis and Rheumatism.  44:1555-1567. 2001
    2001 Recombinant adenovirus expressing adeno-associated virus cap and rep proteins supports production of high-titer recombinant adeno-associated virus 2001
    2001 Aged mice exhibit in vivo defective peripheral clonal deletion of Db/H-Y reactive CD8+ T cellsMechanisms of Ageing and Development.  122:305-326. 2001
    2001 Treatment of chronic sialadenitis in a murine model of Sjögren's syndrome by local fasL gene transferArthritis and Rheumatism.  44:964-973. 2001
    2001 Treatment of chronic sialadenitis in a murine model of Sjögren's syndrome by local fasL gene transfer.Arthritis and Rheumatism.  44:964-973. 2001
    2001 Mutation of the hematopoietic cell phosphatase (Hcph) gene is associated with resistance to γ-irradiation-induced apoptosis in Src homology protein tyrosine phosphatase (SHP)-1-deficient "motheaten" mutant miceJournal of Immunology.  166:772-780. 2001
    2001 Apoptosis and rheumatoid arthritis: past, present, and future directions.Current Rheumatology Reports.  3:70-78. 2001
    2001 The Fas signaling connection between autoimmunity and embryonic lethalityJournal of Clinical Immunology.  21:1-14. 2001
    2000 Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor α and reduces arthritisHuman Gene Therapy.  11:2431-2442. 2000
    2000 Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand-deficient miceJournal of Clinical Investigation.  105:813-821. 2000
    1999 Apoptosis and cell death in the endocrine system 1999
    1999 Herpes simplex virus type 2 infection induced apoptosis in peritoneal macrophages independent of Fas and tumor necrosis factor-receptor signalingViral Immunology.  12:263-275. 1999
    1999 Polyamine-fas interactions: Inhibition of polyamine biosynthesis in MRL-lpr/lpr mice is associated with the up-regulation of fas mRNA in thymocytesAutoimmunity.  29:299-309. 1999
    1999 Regulation of Fas-mediated apoptosis in CD2-fas transgenic miceInternational Reviews of Immunology.  18:309-327. 1999
    1998 Increased susceptibility to apoptosis induced by anti-Fas antibody in a Rothmund-Thomson syndrome lymphoblastoid cell lineProceedings of the Association of American Physicians.  110:218-225. 1998
    1997 Cell death and longevity: Implications of Fas-mediated apoptosis in T-cell senescenceImmunological Reviews.  160:19-30. 1997
    1997 Increased Acute-Phase Response and Renal Amyloidosis in Aged CD2-fas-Transgenic MiceJournal of Immunology.  158:5988-5996. 1997
    1997 Increased apoptosis of CD45RO- T cells with agingMechanisms of Ageing and Development.  94:123-134. 1997
    1997 Clinical features associated with correction of T-cell senescence: Increased acute-phase response, amyloidosis and arthritisDevelopmental and Comparative Immunology.  21:509-523. 1997
    1996 CD2-FAS transgene increases t cell immune response and elevates amyloidosis in the kidney of aged CD-I miceThe FASEB Journal.  10. 1996
    1995 Cyclins and autoimmunity: Cyclin b1 gene expression and restriction fragment length polymorphism in lupus-prone miceAutoimmunity.  22:17-26. 1995
    1994 Regulation of ornithine decarboxylase in the kidney of autoimmune mice with the lpr geneAutoimmunity.  19:253-264. 1994
    1993 Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis reveal a post-transcriptional modification of the enzymeAgents and actions.  39. 1993
    1992 Ethanol intake in the chicken and its effect on body temperature and hypothalamic serotoninNutrition Research.  12:629-642. 1992
    1991 Roles of in vitro- and in vivo-administered histamine and serotonin in compound 48/80-induced gastric acid secretion in isolated, perfused rat stomachDigestive Diseases and Sciences.  36:1708-1714. 1991
    1991 Suppression of Ethanol Intake in Chickens by Fenfluramine and Dietary TryptophanAlcoholism: Clinical and Experimental Research.  15:1056-1059. 1991
    1990 Inhibition of gastric acid secretion in the rat by high calciumNutrition Research.  10:1441-1453. 1990

    Chapter

    Year Title Altmetric
    2017 Regulation of negative selection in the thymus by cytokines: Novel Role of IL-23 to Regulate RORγt.  41-52. 2017
    2009 Gene therapy and immune senescence.  1629-1646. 2009

    Research Overview

  • 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
  • Education And Training

  • Doctor of Philosophy in Nutrition Sciences, Rutgers University : New Brunswick 1995
  • Full Name

  • Hui-Chen Hsu
  • Fax

  • 205-975-6648