Kallistatin Attenuates Experimental Autoimmune Uveitis by Inhibiting Activation of T Cells.

Fauziyya Muhammad,Priscilla N Avalos,Darren J Lee,Jian-Xing Ma,Michelle C Callegan,M H Mursalin

doi:10.3389/fimmu.2020.00975

Abstract

Experimental autoimmune uveoretinitis (EAU) is a mouse model of human autoimmune uveitis. EAU spontaneously resolves and is marked by ocular autoantigen-specific regulatory immunity in the spleen. Kallikrein binding protein (KBP) or kallistatin is a serine proteinase inhibitor that inhibits angiogenesis and inflammation, but its role in autoimmune uveitis has not been explored. We report that T cells activation is inhibited and EAU is attenuated in human KBP (HKBP) mice with no significant difference in the Treg population that we previously identified both before and after recovery from EAU. Moreover, following EAU immunization HKBP mice have potent ocular autoantigen specific regulatory immunity that is functionally suppressive.

Highlights

Uveitis is the third leading cause of blindness in Western countries, with an incidence between 25.6–122 cases per 100,000 a year, and a prevalence of 69–623 cases per 100,000 [1,2,3,4]
This inhibition of T cell activation and the anti-inflammatory properties of kallistatin [23] prompted us to ask if it suppresses experimental autoimmune uveitis (EAU)
TG-human KBP (HKBP) mice have been previously characterized in studies related to diabetic retinopathy, and serum kallistatin in these mice is over four-fold higher than the endogenous mouse kallistatin [31, 32]

Summary

Introduction

Uveitis is the third leading cause of blindness in Western countries, with an incidence between 25.6–122 cases per 100,000 a year, and a prevalence of 69–623 cases per 100,000 [1,2,3,4]. 17.6% of active uveitis patients experience transient or permanent vision loss [6], so a proper diagnosis and treatment are crucial for maintaining vision. Corticosteroids are the first line of treatment for uveitis patients, but due to the myriad of side-effects they are not a long-term treatment option [7,8,9]. Immunosuppressive medications are used to control uveitis, with the goal of sustained remission [10,11,12,13,14,15]. Not all the immunosuppressive medications are effective and some chronic uveitis patients fail multiple treatment regimens. Additional immunosuppressive treatment options are necessary for the treatment of autoimmune uveitis

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Results

Conclusion