Suppressors of Cytokine Signalling (SOCS) have Neuroprotective Roles in Retina

Egwuagu, Charles E.

Abstract

In this study we have investigated the involvement of SOCS proteins in regulating ocular inflammatory diseases of infectious or autoimmune etiology. We recently showed that SOCS3 deletion in T Lymphocytes suppresses the development of chronic ocular inflammation by up-regulating CTLA-4 and inducing the expansion of regulatory T cells. In ongoing studies we are using transgenic rats that over-express SOCS1 in the retina and mice with targeted deletion of SOCS1 in the retina to further elucidate the role of SOCS1 and SOCS3 in ocular diseases. Thus far, our data have revealed that topical SOCS1 antagonists can be useful in suppressing ocular HSV-1 infection and mitigating herpetic stromal keratitis. On the other hand, topical administration of a SOCS1 mimetic peptide inhibits ocular inflammation and mitigates ocular pathology during mouse uveitis

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Eye Institute (NEI)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAEY000280-24
• Application #: 9155551
• Support Year: 24
• Fiscal Year: 2015

Institution

• Name: U.S. National Eye Institute

Publications

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) 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

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

Egwuagu, Charles E (2014) Chronic intraocular inflammation and development of retinal degenerative disease. Adv Exp Med Biol 801:417-25

Yu, Cheng-Rong; Kim, Sung-Hye; Mahdi, Rashid M et al. (2013) SOCS3 deletion in T lymphocytes suppresses development of chronic ocular inflammation via upregulation of CTLA-4 and expansion of regulatory T cells. J Immunol 191:5036-43

Yu, Cheng-Rong; Mahdi, Rashid R; Oh, Hyun-Mee et al. (2011) Suppressor of cytokine signaling-1 (SOCS1) inhibits lymphocyte recruitment into the retina and protects SOCS1 transgenic rats and mice from ocular inflammation. Invest Ophthalmol Vis Sci 52:6978-86