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The research carried out by the Section addresses issues related to mechanisms, cells and molecules that participate in the induction or modulation of ocular inflammation. This Section is part of the Laboratory of Immunology.
The research carried out by the Section addresses issues related to mechanisms, cells and molecules that participate in the induction or modulation of ocular inflammation. We are using the following animal models for ocular inflammation: (i) experimental autoimmune uveitis (EAU), that is actively induced in rodents by immunization with retinal antigens, mostly IRBP or S-antigen, or uveitogenic peptides from their sequence; (ii) ocular inflammation that is induced in transgenic mice expressing hen egg lysozyme (HEL) in their eyes, by adoptively transferring populations of T-cells specific against HEL. The scientific issues currently being addressed include: (1) mechanisms whereby naïve T-cells are activated to acquire pathogenic capacity and the role played by microbial products in these processes; (2) the pathogenic capacity of Th17 cells and their involvement in inflammatory eye disease; (3) differences between the kinetics of pathogenic processes mediated by Th1 or Th17 cells; (4) plasticity of T-cell subsets; (5) subpopulations of Th17 differing in their pathogenic capacity and other biological features; (6) generation of “Th9” populations and analysis of their unique features; (7) modulation of ocular inflammation by immunosuppressive compounds.
Cox, C.A., Shi, G., Yin, H., Vistica, B.P., Wawrousek, E.F., Chan, C.-C., and Gery, I.: Both Th1 and Th17 are immunopathogenic but differ in other key biological activities. J. Immunol., 180:7414-7422, 2008. .Shi, G., Cox, C.A., Vistica, B.P., Tan, C., Wawrousek, E.F., and Gery, I.: Phenotype switching by inflammation-inducing polarized Th17 cells, but not by Th1 cells. J. Immunol., 181:7205-7213, 2008. PMC 2665021 Montalvo, V., and Gery, I.: Constitutive pro-apoptotic molecules are differentially expressed in the fetal and adult mouse eye. Curr. Eye Res., 34:328-332, 2009. PMC 2671852 Fujimoto, C., Klinman, D.M., Shi, G., Yin, H., Vistica, B.P., Lovaas, J.D., Wawrousek, E.F., Igarashi, T., Chan, C.-C., and Gery, I.: A suppressive oligodeoxynucleotide inhibits ocular inflammation. Clin. Exp. Immunol. 156:528-534, 2009. PMC 2691983 Yin, H., Vistica, B.P., Chan, C.-C., Strominger, J.L., and Gery, I.: Inhibition of experimental autoimmune uveitis by amino acid copolymers. J. Neuroimmunol. 215:43-48, 2009. PMC 2928056 Shi, G., Ramaswamy, M., Vistica, B.P., Cox, C.A., Tan, C., Wawrousek, E. F., Siegel, R.M., and Gery, I.: Unlike Th1, Th17 cells mediate sustained autoimmune inflammation and are highly resistant to restimulation-induced cell death. J. Immunol. 183:7547-7556, 2009. PMC 2958176 Tan, C., Aziz, M.K., Lovaas, J.D., Vistica, B.P., Shi, G., Wawrousek, E.F., and Gery, I.: Antigen-specific Th9 cells exhibit uniqueness in their kinetics of cytokine production and short retention at the inflammatory site. J. Immunol. 185:6795-6801, 2010. PMC 2988091 Tan, C., Ramaswamy, M, Shi, G., Vistica, B.P., Siegel, R.M. and Gery, I.: Inflammation-inducing Th1 and Th17 cells differ in their expression patterns of apoptosis-related molecules. (Rapid Communication) Cell. Immunol. 271:210-213, 2011. PMC 3249224 Shi, G. Lovaas, J.D., Tan, C., Vistica, B.P., Wawrousek, E.F., Aziz, M.K., Rigden, R.C., Caspi, R.R., and Gery, I.: Cell-cell interaction with APC, not IL-23, is required for naive CD cells to acquire pathogenicity during Th17 lineage commitment. J. Immunol. 189:1220-1227, 2012. PMC 3401365 Vistica, B.P., Shi, G., Nugent, L., Tan, C., Altman. A., and Gery, I.: SLAT/Def6 plays a critical role in the pathogenic process of experimental autoimmune uveitis (EAU). Molecular Vision, 18:1858-1864, 2012. PMC 3398495 Shi, G., vistica, B.P., Nugent, L.F., Tan, C, Wawrousek, E.F., Klinman, D.M., Gery, I.: Differential Involvement of Th1 and Th17 in Pathogenic Autoimmune Processes Triggered by Different TLR Ligands. J. Immunol., 191:415-423, 2013. Montalvo, V., Quigley, L., Vistica, B.P., Boelte, K.C., Nugent, L.F., Takai, T., McVicar, D.W., Gery, I.: Environmental Factors Determine DAP12 Deficiency To Either Enhance or Suppress Immunopathogenic Processes. Immunology, 140:475-482, 2013. Nugent, L.F., Shi, G, Vistica, B.P., Ogbeifun, O., Hinshaw, S.J.H., Gery, I.: ITE, a novel endogenous nontoxic aryl hydrocarbon receptor ligand, efficiently suppresses EAU and T-cell mediated immunity, Invest. Ophthalmol. Vis. Sci., 54:7463-7469, 2013. Tan, C., Wei, L., Vistica, B.P., Shi, G., Gery, I.: Phenotypes of Th lineages generated by the commonly used activation with anti-CD3/CD28 antibodies differ from those generated by the physiological activation with the specific antigen. Cellular & Molecular Immunology, 11:305-313, 2014. Zhao, C., Shi, G., Vistica, B., Tan, C., Zhang, M., Gery, I.: Induced Regulatory T-cells (iTregs) Generated by Activation with Anti-CD3/CD28 Antibodies Differ From Those Generated by The Physiological-like Activation with Antigen/APC. Cellular Immunology, 290:179-184, 2014. Aug;290(2):179-84. doi: 10.1016/j.cellimm.2014.06.004) Gery, I.: The definition of lymphocyte activating factor: giving a helping hand to serendipity. Front. Immunol. 5:610, 2014. (doi: 10.3389/fimmu.2014.00610) Shi, G.,Chen, S., Wandu, W.S., Ogbeifun, O., Nugent, L.F., Maminishkis, A, Hinshaw, S.J.H., Rodriguez, I.R. Gery. I.: Inflammasomes Induced by 7-Ketocholesterol and Other Stimuli in RPE and in Bone Marrow-Derived Cells Differ Markedly in Their Production of IL-1and IL-18. Inveset. Ophthalmol. Vis. Sci. 56: 1658-1664, 2015. Wandu, S,W., Tan, C., Ogbeifun, O., Vistica, B.P., Shi, G., Hinshaw, S.J.H., Xie, C., Chen, X., Klinman, D.M., Cai, H., Gery, I.: Leucine-rich repeat kinase 2 (LRRK2) deficiency diminishes the development of experimental autoimmune uveitis (EAU) and the adaptive immune response. PLoS ONE, 10(6): e0128906. 2015. doi:10.1371/journal. Pone.0128906. Hinshaw, S.J.H., Ogbeifun, O., Wandu, W. S., Lyu, C., Shi, G., Li, Y., Qian, H., Gery, I. Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes Severe Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. In press
|Igal Gery, Ph.D.
|Barbara P. Vistica, M.S||Microbiologistfirstname.lastname@example.org|
|Guangpu Shi, M.D.||Research email@example.com|
|Cuiyan Tan, Ph.D.||Visiting Fellow||Tancu@nei.nih.gov|
|Wambui S. Wandu||Contractorfirstname.lastname@example.org|
|Cancan Lyu, M.D.||Special Volunteer||Cancanlyu@nih.gov|