A Potential of sFasL in Preventing Gland Injury in Sjogren's Syndrome.

Jiao Luo,Hongyan Qian,Bing Yu,Yan He,Guixiu Shi,Ying Wang

doi:10.1155/2017/5981432

Abstract

Fas and its ligand FasL, members of tumor necrosis factor receptor superfamily, have been implicated in the process of cell apoptosis. FasL consists of two forms, membrane FasL (mFasL) and soluble FasL (sFasL). sFasL can be produced by mFasL cleaved by matrix metalloproteinases (MMP) and also reveals a role for binding to Fas which is expressed on cell surface. Although Fas/FasL axis has been implicated in a variety of diseases, its role in Sjogren's syndrome still remains ill defined. In this study, we investigated the potential of sFasL in the pathogenesis of Sjogren's syndrome (SS). We found that the serum levels of sFasL in SS patients were significantly lower than healthy subjects. Moreover, serum levels of sFasL in patients with mild disease activity were higher than patients with severe disease activity. There is a positive correlation of the serum level of sFasL with uptake index of parotid gland in our expectation. In addition, liver injury involvement in SS patients showed decreased level of sFasL. Furthermore, we here also observed that the protective cytokine IL-10 expression was positively correlated with sFasL expression. Thus, our results here suggest a potential of sFasL in maintaining gland organ homeostasis.

Highlights

Sjogren’s syndrome (SS) is a chronic autoimmune disease that resulted from immune tolerance breakdown, leading to lymphocytes infiltration in gland organs and immune complex deposition as a consequence of B cell hyperactivity [1,2,3]
Fas and its ligand (FasL) can be catalyzed by matrix metalloproteinases (MMP) from membranes, which lead to a soluble form soluble FasL (sFasL) [15]. sFasL could induce apoptosis of cells when it binds to Fas which is expressed on cell surface
We found that serum levels of sFasL were significantly lower in SS patients with mild disease activity, and the levels of sFasL exhibited a positive correlation with uptake index of parotid gland

Summary

Introduction

Sjogren’s syndrome (SS) is a chronic autoimmune disease that resulted from immune tolerance breakdown, leading to lymphocytes infiltration in gland organs (salivary gland, lachrymal gland, and the liver) and immune complex deposition as a consequence of B cell hyperactivity [1,2,3]. The extracellular domain is responsible for binding to its receptor Fas. FasL induces apoptotic death of sensitive lymphoid cells expressing its cell surface receptor [9]. Activated T and B lymphocytes express Fas receptor and are sensitive to Fas receptor mediated apoptosis [9, 10] This has been proposed to be responsible for several regulatory functions of the immune system, including tolerance acquisition, downregulation of immune reactions, and clonal deletion of peripheral lymphocytes [11,12,13,14]. Excessive expression of FasL can inhibit some autoimmune diseases by deleting autoreactive immune cells [16, 17]

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Conclusion