Mechanisms of immune homeostasis and regulation of intraocular inflammation

Egwuagu, Charles E.

Abstract

Our research focused on 3 broad themes: (i) Etiology and pathogenesis of ocular inflammatory diseases. (ii) Development of Biologics for treating autoimmune diseases; (iii) T cell and cytokine biology: Contributions to basic mechanisms of host immunity. Significant advances in each of these areas include: 1. Discovery that Interleukin-35 induces regulatory B cells that suppress autoimmune disease. 2. Characterization of factors that underlie the development of chronic intraocular inflammation and retinal degenerative disease. (3) Demonstration of the critical roles of IRF-8, STAT3, SOCS1, cytokines in the development and suppression uveitis.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Eye Institute (NEI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAEY000372-16
• Application #: 9362372
• Support Year: 16
• Fiscal Year: 2016

Institution

• Name: U.S. National Eye Institute

Publications

Yu, Cheng-Rong; Choi, Jin Kyeong; Uche, Anita N et al. (2018) Production of IL-35 by Bregs is mediated through binding of BATF-IRF-4-IRF-8 complex to il12a and ebi3 promoter elements. J Leukoc Biol 104:1147-1157

Wan, Chi-Keung; He, Chang; Sun, Lin et al. (2016) Cutting Edge: IL-1 Receptor Signaling is Critical for the Development of Autoimmune Uveitis. J Immunol 196:543-6

Wang, Xiaoqian; Wei, Yinxiang; Xiao, He et al. (2016) A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice. Eur J Immunol 46:1343-50

Sun, Lin; St Leger, Anthony J; Yu, Cheng-Rong et al. (2016) Interferon Regulator Factor 8 (IRF8) Limits Ocular Pathology during HSV-1 Infection by Restraining the Activation and Expansion of CD8+ T Cells. PLoS One 11:e0155420

He, Chang; Yu, Cheng-Rong; Mattapallil, Mary J et al. (2016) SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis). Mediators Inflamm 2016:2939370

Wang, Xiaoqian; Wei, Yinxiang; Xiao, He et al. (2016) Pre-existing CD19-independent GL7(-) Breg cells are expanded during inflammation and in mice with lupus-like disease. Mol Immunol 71:54-63

Egwuagu, C E; Sun, L; Kim, S-H et al. (2015) Ocular Inflammatory Diseases: Molecular Pathogenesis and Immunotherapy. Curr Mol Med 15:517-28

He, Chang; Yu, Cheng-Rong; Sun, Lin et al. (2015) Topical administration of a suppressor of cytokine signaling-1 (SOCS1) mimetic peptide inhibits ocular inflammation and mitigates ocular pathology during mouse uveitis. J Autoimmun 62:31-8

Yu, Cheng-Rong; Hayashi, Kozaburo; Lee, Yun Sang et al. (2015) Suppressor of cytokine signaling 1 (SOCS1) mitigates anterior uveitis and confers protection against ocular HSV-1 infection. Inflammation 38:555-65

Kim, Sung-Hye; Burton, Jenna; Yu, Cheng-Rong et al. (2015) Dual Function of the IRF8 Transcription Factor in Autoimmune Uveitis: Loss of IRF8 in T Cells Exacerbates Uveitis, Whereas Irf8 Deletion in the Retina Confers Protection. J Immunol 195:1480-8