Experimental Immunology Section
Research
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.
Staff
| Name | Title | |
|---|---|---|
Igal Gery, Ph.D. |
Section Head | geryi@nei.nih.gov |
| Barbara P. Vistica, M.S | Microbiologist | visticab@nei.nih.gov |
| Guangpu Shi, M.D. | Research fellow | shig@nei.nih.gov |
| Cuiyan Tan, Ph.D. | Visiting Fellow | Tancu@nei.nih.gov |
| Mehak Aziz, B.A. | Post-bac IRTA Fellow | azizmk@nei.nih.gov |
Recent Publications
Zhang, M., Chan, C.-C., Vistica, B., Hung, V., Wiggert, B., and Gery, I.: Copolymer 1 inhibits experimental autoimmune uveoretinitis. J. Neuroimmunol. 103:189-194, 2000. PubMed
Kozhich, A.T., Chan, C.-C., Gery, I., and Whitcup, S.M.: Recurrent intraocular inflammation in endotoxin-induced uveitis. Invest. Ophthalmol. Vis. Sci. 41:1823-1826, 2000. PubMed
de Vos, A.F., Fukushima, A., Lobanoff, M.C., Vistica, B.P., Lai, J.C., Grivel, J.-C., Wawrousek, E.F., Whitcup, S.M., and Gery, I. Breakdown of tolerance to a neo-self antigen in double transgenic mice in which B cells present the antigen. J. Immunol. 164:4594-4600, 2000. PubMed
Gelderman, M.P., Gonzalez-Fernandez, F., Baer, C.A., Wiggert, B., Chan, C.-C., Vistica, B.P., and Gery, I.: Xenopus IRBP, a phylogenetically remote protein, is uveitogenic in Lewis rats. Exp. Eye Res. 70:731-736, 2000. PubMed
Zhang, M., Vacchio, M.S., Vistica, B.P., Lesage, S., Egwuagu, C.E., Yu, C.-R., Gelderman, M.P., Kennedy, M.C., Wawrousek, E.F., and Gery, I.: T cell tolerance to a neo-self antigen expressed by thymic epithelial cells: The soluble form is more effective than the membrane-bound form. J. Immunol., 170:3954-3962, 2003. PubMed
Gelderman, M.P., Charukamnoetkanok, P., Brady, J.P., Hung, L., Zigler, J.S., Jr., Wawrousek, E.F., Vistica, B.P., Fortin. E., Chan, C.-C., and Gery, I.: A novel inflammatory eye disease induced by lymphocytes from knockout mice sensitized against the deleted ocular antigen. Clin. Exp. Immunol., 133:177-181, 2003. PubMed
Yu, C.-R., Mahdi, R.M., Ebong, S., Vistica, B.P., Gery, I., and Egwuagu, C.E.: Suppressor of cytokine signaling 3 regulates proliferation and activation of T-helper cells. J. Biol. Chem., 278:29752-29579, 2003. PubMed
Charukamnoetkanok, P., Brady, J.P., Wawrousek, E.F., Egwuagu, C.E., Zigler, J.S., Jr., Vistica, B.P., Whitcup, S.M., and Gery, I.: Immunotolerance toward native aA-crystallin in knockout mice deficient in the functional protein. Immunol. Lett., 89:259-265, 2003. PubMed
Ham, D.-I. Kim, S., Chen, J., Vistica, B.P., Farris, R.N., Lee, R.S., Wawrousek, E.F., Takase, H., Yu, C.-R., Egwuagu, C.E., Chan, C.-C., and Gery, I.: Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter. Invest. Ophthalmol. Vis. Sci., 45:857-862, 2004. PubMed
Yu, C.-R., Mahdi, R.M., Ebong, S., Vistica, B.P., Chen, J., Guo, Y., Gery, I. and Egwuagu, C.E.: Proliferation and STAT6 Signaling Pathways are Negatively Regulated in T-helper Cells by STAT1 and Suppressors of Cytokine Signaling (SOCS). J. Immunol., 173: 737-746, 2004. PubMed
Tuo, J., Smith, B., Chew, E., Bojanowski. C.M., Meleth, A.D., Csaky, K., Gery, I. and Chan, C.-C.: The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration. FASEB J. 18:1297-1299, 2004. PubMed
Chen, J., Vistica, B.P., Takase, H., Ham, D.-I., Fariss, B.N., Wawrousek, E.F., Chan, C.-C., DeMartino, J.A., Farber, J.M. and Gery, I.: A unique pattern of up- and down-regulation of chemokine receptor CXCR3 on inflammation-inducing Th1 cells. Europ. J. Immunol. 34:2885-2894, 2004. PubMed
Ledee, D.R., Chen, J., Tonelli, L.H., Takase, H., Gery, I. and Zelenka, P.: Differential expression of splice variants of chemokine CCL27 mRNA in lens, cornea, and retina of the normal mouse eye. Mol. Vis. 10:663-667, 2004. PubMed
Chen, J., Vistica, B.P., Wiggert, B., Chan, C.-C., and Gery, I: The immunomodulator vasoactive intestinal peptide (VIP) does not affect experimental autoimmune uveitis (EAU) in B10.RIII mice. Ocul. Immunol. Inflam., 13:13-17, 2005. PubMed
Lim, W.-K., Fujimoto, C., Ursea, R., Mahesh, S.P., Silver, P., Chan, C.-C., Gery, I., and Nussenblatt, R.B.: Interleukin-1 receptor antagonist suppresses immune-mediated ocular inflammation in mice. Arch. Ophthalmol., 123:957-963, 2005. PubMed
Takase, H., Yu, C.-R., Mahdi, R.M., Douek, D.C., DiRusso, G.B., Midgley, F.M., Dogra, R., Allende, G., Rosenkranz, E., Pugliese, A., Egwuagu, C.E., and Gery, i.: Thymic expression of peripheral tissue antigens in humans:a remarkable variability among individuals. Inter. Immunol., 17:1131-1140, 2005. PubMed
Takase, H., Yu, C.-R., Liu, X., Fujimoto, C., Gery, I. And Egwuagu, C.E.: Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): Potential neuroprotective role of SOCS proteins. J. Neuroimmunol., 168:118-127, 2005 PubMed
Takase, H., Yu, C.-R., Ham, D.-I., Chan, C.-C., Chen, J., Vistica, B.P., Wawrousek, E.F., Durum, S.K., Egwuagu, C.E., and Gery, I.: Inflammatory processes triggered by TCR engagement or by local cytokine expression: Differences in profiles of gene expression and infiltrating cell populations. J. Leuk. Biol., 80:538-545, 2006. PubMed
Ham, D.-I., Fujimoto, C., Gentleman, S., Chan, C.-C., Yu, C.-R., Yu, S., Egwuagu, C.E., Redmond, T.M., and Gery, I.: The level of thymic expression of RPE65 inversely correlates with its capacity to induce experimental autoimmune uveitis (EAU) in different rodent strains. Exp. Eye Res., 83:897-902, 2006. PubMed
Chen, J., Fujimoto, C., Vistica, B.P., Wawrousek, E.F., Kelsall, B., and Gery, I.: Active participation of antigen-nonspecific lymphoid cells in immune-mediated inflammation. J. Immunol., 177:3362-3368, 2006. PubMed
Hikita, S.T., Vistica, B.P., Jones, H.R., Keswani, J.R., Watson, M.M., Ericson, V.R., Ayoub, G.S., Gery, I., and Clegg, D.O: Osteopontin is pro-inflammatory in experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci., 47:4435-4443, 2006. PubMed
Fujimoto, C., Yu, C.-R., Shi, G., Vistica, B.P., Wawrousek, E.F., Klinman, D.M., Chan, C.-C., Egwuagu, C.E., and Gery, I.: Pertussis toxin is superior to TLR ligands in enhancing pathogenic autoimmunity, targeted at a neo-self antigen, by triggering robust expansion of Th1 cells and their cytokine production. J. Immunol. 177:6896-6903, 2006. PubMed
Amadi-Obi, A., Yu, C.-R., Liu, X., Mahdi, R.M, Levy-Clark, G., Nussenblatt, R.B., Gery, I., Lee, Y.S. and Egwuagu, C.E.: Th17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1. Nature Med., 13:711-718, 2007. PubMed
Ganguly, S., Grodzki, C., Sugden, D., Møller, M., Odom, S., Gaildrat, P., Gery, I., Siraganian, R.P., Rivera, J., and Klein, D.C.: Neural adrenergic/cyclic AMP regulation of the immunoglobulin E receptor -subunit expression in the mammalian pinealocyte. A neuroendocrine/immune response link? J. Biol. Chem., 282:32758-32764, 2007. PubMed
Montalvo, V., Campos, M.M., Chan, C.-C.,. Wawrousek, E.F., Bush, R.A., Lambris, J.D., and Gery, I.: Complement deposits on ocular tissues adjacent to sites of inflammation. Curr. Eye Res., 32:917-922, 2007 (Erratum, correcting authors' order: 33:109, 2008). PubMed
Fujimoto, C., Shi, G. and Gery, I.: Microbial products trigger autoimmune ocular inflammation. Ophthalmic Res., 40:193-199, 2008. PubMed
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. PubMed
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. PubMed
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. PubMed
Gery, I. and Chan, C-C.: Mechanism of uveitis. In: Ophthalmology, 3rd edition Yanoff and Duker, Mosby/Elsevier, pp 777-782, 2009.
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.
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. PubMed
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. In press.
