NK cells are negatively regulated by sCD83 in experimental autoimmune uveitis

Wei Lin,Yufei Sun,Nannan Song,Xuejing Man,Yingying Yue,Peng Li,Bingqing Li,Yuanbin Li,Qiang Fu

doi:10.1038/s41598-017-13412-1

Abstract

Natural killer (NK) cells represent a subset of lymphocytes that contribute to innate immunity and have been reported to play a role in autoimmune uveitis. However, the mechanisms regulating NK cellular function in this condition remain unclear. Herein, we investigated the status of NK cells in experimental autoimmune uveitis (EAU). We found that the number of CD83+CD3−NK1.1+ cells was increased in the inflamed eyes and spleens of the EAU mouse model. At the recovery stage of EAU, serum concentrations of soluble CD83 (sCD83) were increased. sCD83 treatment relieved retinal tissue damage and decreased the number of infiltrating NK cells in inflamed eyes. Further analysis of the effects of sCD83 treatment in EAU revealed that it reduced: 1) the expressions of CD11b and CD83 in NK cells, 2) the percent of CD11bhighCD27lowCD3−NK1.1+ cells and 3) the secretion of granzyme B, perforin and IFN-γ in NK cells as demonstrated both in vivo and in vitro. When sCD83 treated-NK cells were transferred into EAU mice, retinal tissue damage was relieved. These results demonstrate sCD83 down-regulate NK cellular function and thus provide important, new information regarding the means for the beneficial effects of this agent in the treatment of autoimmune uveitis.

Highlights

Nature killer (NK) cells are a part of the innate immune system and represent the first line of defense against infections
It has been reported to be a potential therapeutic agent for use in the treatment of autoimmune diseases21–25. soluble CD83 (sCD83) is a soluble molecule that is expressed in the extracellular domain of the membrane-bound CD83 molecule. mCD83 is a member of the immunoglobulin super family which is expressed on many activated cells, such as mature dendritic cells (DCs), activated T cells and B cells, and activated NK cells[21,22,23,26,27]
To assess whether sCD83 treatment changes the secretions of IFN-γ, perforin and granzyme B of NK cells, we examined the secretion of IFN-γ, perforin and granzyme B in NK cells of experimental autoimmune uveitis (EAU) mice following sCD83 treatment

Summary

Introduction

Nature killer (NK) cells are a part of the innate immune system and represent the first line of defense against infections. NK cells have been implicated in the regulatory mechanisms of autoimmune diseases such as diabetes and insulitis, rheumatoid arthritis, experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune uveitis (EAU)[1,2,3,4,5] Findings from these studies have resulted in the hypothesis that NK cells may change the balance of immunity in autoimmune diseases by regulating the secretion of cytokines or by interacting with other cells[1,4,6,7,8,9,10]. The expression of surface molecules on NK cells, including activating signals, inhibitory signals, mature makers and adhesion molecules, can all act as important factors in determining NK cellular functions[11]. The results from our studies support the hypothesis that sCD83 might be a potential therapeutic agent for use in the treatment of EAU

Methods

Results

Conclusion