Jun Tang
National Institutes of Health
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Publication
Featured researches published by Jun Tang.
Journal of Experimental Medicine | 2008
Dror Luger; Phyllis B. Silver; Jun Tang; Daniel J. Cua; Zoe Chen; Yoichiro Iwakura; Edward P. Bowman; Nicole Sgambellone; Chi-Chao Chan; Rachel R. Caspi
Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans. We examined the role of the interleukin (IL)-23–IL-17 and IL-12–T helper cell (Th)1 pathways in the pathogenesis of EAU. IL–23 but not IL-12 was necessary to elicit disease by immunization with the retinal antigen (Ag) interphotoreceptor retinoid-binding protein (IRBP) in complete Freunds adjuvant. IL-17 played a dominant role in this model; its neutralization prevented or reversed disease, and Th17 effector cells induced EAU in the absence of interferon (IFN)-γ. In a transfer model, however, a polarized Th1 line could induce severe EAU independently of host IL-17. Furthermore, induction of EAU with IRBP-pulsed mature dendritic cells required generation of an IFN-γ–producing effector response, and an IL-17 response by itself was insufficient to elicit pathology. Finally, genetic deficiency of IL-17 did not abrogate EAU susceptibility. Thus, autoimmune pathology can develop in the context of either a Th17 or a Th1 effector response depending on the model. The data suggest that the dominant effector phenotype may be determined at least in part by conditions present during initial exposure to Ag, including the quality/quantity of Toll-like receptor stimulation and/or type of Ag-presenting cells. These data also raise the possibility that the nonredundant requirement for IL-23 in EAU may extend beyond its role in promoting the Th17 effector response and help provide a balance in the current Th1 versus Th17 paradigm.
Journal of Immunology | 2009
Jun Tang; Ru Zhou; Dror Luger; Wei Zhu; Phyllis B. Silver; Rafael S. Grajewski; Shao-Bo Su; Chi-Chao Chan; Luciano Adorini; Rachel R. Caspi
Experimental autoimmune uveitis (EAU) serves as a model for human autoimmune uveitis and for cell-mediated autoimmunity in general. EAU induced in mice by immunization with the retinal Ag interphotoreceptor retinoid-binding protein in CFA is driven by the Th17 response. Oral calcitriol (1,25-dihydroxyvitamin D3) prevented as well as partly reversed disease and suppressed immunological responses. In vitro, calcitriol directly suppressed IL-17 induction in purified naive CD4+ T cells without inhibiting Th17 lineage commitment, as reflected by unaltered RORγt, STAT3, and FoxP3 expression. In contrast, in vivo treatment with calcitriol of mice challenged for EAU impaired commitment to the Th17 lineage, as judged by reduction of both RORγt and IL-17 in CD4+ T cells. Innate immune response parameters in draining lymph nodes of treated mice were suppressed, as was production of IL-1, IL-6, TNF-α, and IL-12/IL-23p40, but not IL-10, by explanted splenic dendritic cells (DC). Finally, supernatants of calcitriol-conditioned bone marrow-derived DC had reduced ability to support Th17 polarization of naive CD4+ T cells in vitro and in vivo. Thus, calcitriol appears to suppress autoimmunity by inhibiting the Th17 response at several levels, including the ability of DC to support priming of Th17 cells, the ability of CD4+ T cells to commit to the Th17 lineage, and the ability of committed Th17 T cells to produce IL-17.
Journal of Immunology | 2005
Shao Bo Su; Phyllis B. Silver; Rafael S. Grajewski; Rajeev K. Agarwal; Jun Tang; Chi-Chao Chan; Rachel R. Caspi
Induction of tissue-specific experimental autoimmune diseases involves an obligatory adjuvant effect to trigger an innate response of a type that will drive a Th1-biased adaptive response. This is achieved by use of CFA containing mycobacteria (Mycobacterium tuberculosis), whose recognition by cells of the innate immune system depends on TLRs that signal through the adaptor molecule MyD88. We examined the role of selected components of the MyD88 pathway in promoting experimental autoimmune uveitis (EAU). Mice deficient in MyD88, TLR2, TLR4, or TLR9 were immunized with the retinal Ag interphotoreceptor retinoid-binding protein in CFA, and their EAU scores and associated immunological responses were examined. MyD88−/− mice were completely resistant to EAU and had a profound defect in Th1, but not Th2, responses to autoantigen challenge. Surprisingly, TLR2−/−, TLR4−/−, and TLR9−/− mice were fully susceptible to EAU and had unaltered adaptive responses to interphotoreceptor retinoid-binding protein. Examination of IL-1R family members, which share the common adaptor MyD88 with the TLR family, revealed that IL-1R-deficient mice, but not IL-18-deficient mice, are resistant to EAU and have profoundly reduced Th1 and Th2 responses. These data are compatible with the interpretation that TLR9, TLR4, and TLR2 signaling is either not needed, or, more likely, redundant in the adjuvant effect needed to induce EAU. In contrast, signaling through the IL-1R plays a necessary and nonredundant role in EAU and can by itself account for the lack of EAU development in MyD88 mice.
Journal of Immunology | 2007
Jun Tang; Wei Zhu; Phyllis B. Silver; Shao-Bo Su; Chi-Chao Chan; Rachel R. Caspi
Human autoimmune uveitis is a heterogeneous group of potentially blinding ocular diseases in which most patients who exhibit immunity recognize the same retinal Ag. It is represented by the model of experimental autoimmune uveitis (EAU) induced in mice by immunization with retinal Ag in CFA. Murine EAU is characterized by a Th1/Th17 response pattern, which may not represent all types of human uveitis. We report in this study a new model of EAU induced by injection of matured dendritic cells loaded with a uveitogenic retinal peptide. Dendritic cell-induced EAU demonstrated unique characteristics compared with traditional EAU in terms of clinical manifestations, the nature of the inflammatory infiltrating cells, the cytokine response profile, and a strict requirement for IFN-γ, whereas IL-17 appeared to play a minor role. Disease was self-limiting, but could be reinduced with the same Ag in CFA, albeit with reduced severity, suggesting postrecovery resistance. Our study demonstrates in a disease setting that the context in which the same autoantigen is initially presented to the immune system precipitates distinct forms of pathology via a distinct pathogenic pathway on the same genetic background. These findings may shed new light on the complex biology and the heterogeneous nature of human uveitis, and provide an alternative model for uveitic diseases of immune origin.
Ophthalmic Research | 2008
Rachel R. Caspi; Phyllis B. Silver; Dror Luger; Jun Tang; Lizette M. Cortes; Giuseppina Pennesi; Mary J. Mattapallil; Chi-Chao Chan
The mouse model of experimental autoimmune uveitis, induced by immunization of mice with the retinal protein IRBP, was developed in our laboratory 20 years ago and published in 1988. Since that time it has been adopted by many investigators and has given rise to many studies that helped elucidate genetic influences, dissect the basic mechanisms of pathogenesis and test novel immunotherapeutic paradigms. The current overview will summarize the salient features of the experimental autoimmune uveitis model and discuss its mechanisms.
Investigative Ophthalmology & Visual Science | 2007
Shao Bo Su; Rafael S. Grajewski; Dror Luger; Rajeev K. Agarwal; Phyllis B. Silver; Jun Tang; Jingsheng Tuo; Chi-Chao Chan; Rachel R. Caspi
Journal of Immunology | 2007
Jun Tang; Wei Zhu; Milan R. Uskokovic; Phyllis Sliver; Shao-Bo Su; Chi-Chao Chan; Luciano Adorini; Rachel R. Caspi
Cytokine | 2007
Dror Luger; Phyllis B. Silver; Jun Tang; Daniel J. Cua; Zoe Chen; Yoichiro Iwakura; Edward P. Bowman; Nicole Sgambellone; Chi-Chao Chan; Rachel R. Caspi
Investigative Ophthalmology & Visual Science | 2006
Wei Zhu; Jun Tang; M.R. Uskokovic; Phyllis B. Silver; Shao-Bo Su; Chi-Chao Chan; L. Adorini; Rachel R. Caspi
Clinical Immunology | 2006
Shao-Bo Su; Rafael S. Grajewski; Rajeev K. Agarwal; Phyllis B. Silver; Jun Tang; Chi-Chao Chan; Rachel R. Caspi