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Citations to this article

A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice
Giuseppina Pennesi, … , Chi-Chao Chan, Rachel R. Caspi
Giuseppina Pennesi, … , Chi-Chao Chan, Rachel R. Caspi
Published April 15, 2003
Citation Information: J Clin Invest. 2003;111(8):1171-1180. https://doi.org/10.1172/JCI15155.
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Article Immunology Article has an altmetric score of 3

A humanized model of experimental autoimmune uveitis in HLA class II transgenic mice

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Abstract

Experimental autoimmune uveitis (EAU) is a disease of the neural retina induced by immunization with retinal antigens, such as interphotoreceptor retinoid-binding protein (IRBP) and arrestin (retinal soluble antigen, S-Ag). EAU serves as a model for human autoimmune uveitic diseases associated with major histocompatibility complex (HLA) genes, in which patients exhibit immunological responses to retinal antigens. Here we report the development of a humanized EAU model in HLA transgenic (TG) mice. HLA-DR3, -DR4, -DQ6, and -DQ8 TG mice were susceptible to IRBP-induced EAU. Importantly, HLA-DR3 TG mice developed severe EAU with S-Ag, to which wild-type mice are highly resistant. Lymphocyte proliferation was blocked by anti-HLA antibodies, confirming that antigen is functionally presented by the human MHC molecules. Disease could be transferred by immune cells with a Th1-like cytokine profile. Antigen-specific T cell repertoire, as manifested by responses to overlapping peptides derived from S-Ag or IRBP, differed from that of wild-type mice. Interestingly, DR3 TG mice, but not wild-type mice, recognized an immunodominant S-Ag epitope between residues 291 and 310 that overlaps with a region of S-Ag recognized by uveitis patients. Thus, EAU in HLA TG mice offers a new model of uveitis that should represent human disease more faithfully than currently existing models.

Authors

Giuseppina Pennesi, Mary J. Mattapallil, Shu-Hui Sun, Dody Avichezer, Phyllis B. Silver, Zaruhi Karabekian, Chella S. David, Paul A. Hargrave, J. Hugh McDowell, W. Clay Smith, Barbara Wiggert, Larry A. Donoso, Chi-Chao Chan, Rachel R. Caspi

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Total citations by year

Year: 2024 2022 2021 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 Total
Citations: 1 2 5 2 1 1 2 7 1 3 3 3 2 1 4 1 1 1 1 42
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Citations to this article (42)

Title and authors Publication Year
Dietary caloric restriction protects experimental autoimmune uveitis by regulating Teff/Treg balance
Li Z, Duan R, Jiang Q, Liu J, Chen J, Jiang L, Wang T, Li H, Zhang Y, Peng X, Huang Z, Zhu L, Zou W, Lin Y, Su W
iScience 2024
Multimodal evaluation of an interphotoreceptor retinoid-binding protein-induced mouse model of experimental autoimmune uveitis
J Yang, K Yun, J Jeon, H Yang, B Kim, S Jeong, J Lee, W Oh, A Uemura, J Song, P Kim, J Lee
Experimental & molecular medicine 2022
Pathogenesis and current therapies for non-infectious uveitis.
Wu X, Tao M, Zhu L, Zhang T, Zhang M
Clinical and Experimental Medicine 2022
A Review of the Various Roles and Participation Levels of B-Cells in Non-Infectious Uveitis
L Zhu, B Chen, W Su
Frontiers in immunology 2021
The Role of Retinal Pigment Epithelial Cells in Regulation of Macrophages/Microglial Cells in Retinal Immunobiology
AW Taylor, S Hsu, TF Ng
Frontiers in immunology 2021
Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice
H Li, L Zhu, R Wang, L Xie, J Ren, S Ma, W Zhang, X Liu, Z Huang, B Chen, Z Li, H Feng, GH Liu, S Wang, J Qu, W Su
Protein & Cell 2021
Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.
Li H, Zhu L, Wang R, Xie L, Chen Y, Duan R, Liu X, Huang Z, Chen B, Li Z, Wang X, Su W
Investigative ophthalmology & visual science 2021
Primed Mycobacterial Uveitis (PMU) as a Model for Post-Infectious Uveitis.
John S, Bell OH, Wilson L, Copland DA, Pepple KL
Journal of visualized experiments : JoVE 2021
Comprehensive analysis of a mouse model of spontaneous uveoretinitis using single-cell RNA sequencing
JS Heng, SF Hackett, GL Stein-OBrien, BL Winer, J Williams, LA Goff, J Nathans
Proceedings of the National Academy of Sciences 2019
Identification of Ocular Autoantigens Associated With Juvenile Idiopathic Arthritis-Associated Uveitis
M Busch, KL Wefelmeyer, K Walscheid, K Rothaus, D Bauer, CA Deeg, RL Degroote, D Ackermann, S König, S Thanos, M Kasper, A Heiligenhaus
Frontiers in immunology 2019
Automated three-dimensional cell counting method for grading uveitis of rodent eye in vivo with optical coherence tomography
WJ Choi, KL Pepple, RK Wang
Journal of Biophotonics 2018
Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site
CR Zárate-Bladés, R Horai, MJ Mattapallil, NJ Ajami, M Wong, JF Petrosino, K Itoh, CC Chan, RR Caspi
Gut microbes 2017
Involvement of B cells in non-infectious uveitis
JR Smith, AJ Stempel, A Bharadwaj, B Appukuttan
IBMS BoneKEy 2016
Suppression and Regulation of Immune Responses: Methods and Protocols, Volume II
MC Cuturi, I Anegon
Suppression and Regulation of Immune Responses 2016
Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitis in vivo : a preliminary study
WJ Choi, KL Pepple, Z Zhi, RK Wang
Journal of Biomedical Optics 2015
Immune mechanisms in inflammatory and degenerative eye disease
VL Perez, RR Caspi
Trends in Immunology 2015
Macrophages and Uveitis in Experimental Animal Models
S Mérida, E Palacios, A Navea, F Bosch-Morell
Mediators of Inflammation 2015
Experimental autoimmune uveitis and other animal models of uveitis: An update
R Agrawal, VA Barathi, D Iwata, S Bansal
Indian journal of ophthalmology 2015
Investigation of the relationship between the onset of arthritis and uveitis in genetically predisposed SKG mice
EJ Lee, EE Vance, BR Brown, PS Snow, JS Clowers, S Sakaguchi, HL Rosenzweig
Arthritis Research & Therapy 2015
Characterization of a New Epitope of IRBP That Induces Moderate to Severe Uveoretinitis in Mice With H-2 b Haplotype
MJ Mattapallil, PB Silver, LM Cortes, AJ st. Leger, Y Jittayasothorn, JL Kielczewski, JJ Moon, CC Chan, RR Caspi
Investigative ophthalmology & visual science 2015
Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function
JL Kielczewski, R Horai, Y Jittayasothorn, CC Chan, RR Caspi
Journal of immunology (Baltimore, Md. : 1950) 2015
Immunotherapeutic strategies in autoimmune uveitis
PH Papotto, EB Marengo, LR Sardinha, AC Goldberg, LV Rizzo
Autoimmunity Reviews 2014
IL-27p28 inhibits central nervous system autoimmunity by concurrently antagonizing Th1 and Th17 responses
WP Chong, R Horai, MJ Mattapallil, PB Silver, J Chen, R Zhou, Y Sergeev, R Villasmil, CC Chan, RR Caspi
Journal of Autoimmunity 2013
Breakdown of immune privilege and spontaneous autoimmunity in mice expressing a transgenic T cell receptor specific for a retinal autoantigen
R Horai, PB Silver, J Chen, RK Agarwal, WP Chong, Y Jittayasothorn, MJ Mattapallil, S Nguyen, K Natarajan, R Villasmil, P Wang, Z Karabekian, SD Lytton, CC Chan, RR Caspi
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Effective Arrestin-Specific Immunotherapy of Experimental Autoimmune Uveitis with RTL: A Prospect for Treatment of Human Uveitis
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Translational Vision Science & Technology 2013
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Proceedings of the National Academy of Sciences 2012
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Autoimmunity 2012
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R Tasso, C Ilengo, R Quarto, R Cancedda, RR Caspi, G Pennesi
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Journal of immunology (Baltimore, Md. : 1950) 2009
Inhibitory peptide analogs derived from a major uveitogenic epitope protect from antiretinal autoimmunity by inducing type 2 and regulatory T cells
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Spontaneous autoimmunity prevented by thymic expression of a single self-antigen
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