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 STAT3, SOCS1, miR155 and CTLA4 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 #: 1ZIAEY000372-14
• Application #: 8938306
• Support Year: 14
• Fiscal Year: 2014

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