A Potential of sFasL in Preventing Gland Injury in Sjogren’s Syndrome

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.

FAS promoter polymorphisms and serum sFas level are associated with increased risk of nerve damage in Bangladeshi patients with Guillain-Barré syndrome

“…Increased serum sFas and sFasL levels have been reported in several immune-mediated diseases [ 12 , 18 ]. In this study, sFas and sFasL were significantly elevated in the pretreatment serum samples of patients with GBS compared to healthy controls.…”

“…The sFas receptor molecule, which is generated by alternative splicing and lacks the transmembrane segment, may contribute to disease pathogenesis by binding to FasL to prevent apoptosis in autoreactive or Fas-expressing lymphocytes [ 17 ]. On the other hand, sFasL is cleaved from membrane-bound FasL by matrix metalloproteinase (MMP), and possesses the ability to induce apoptosis by binding to FasL [ 18 ]. Increased levels of serum sFas and sFasL have been reported in SLE [ 19 ] and may indicate an aberrant immune response characterized by interference with Fas-FasL-mediated apoptosis [ 20 ].…”

Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in Sjögren’s Syndrome

“…However, a recent study [ 61 ] showed that the serum levels of sFasL in patients with SS were significantly lower than those of healthy subjects, and the sFasL levels of the patients in the severe disease activity group were lower than those of the patients in the mild disease activity group. Interestingly, that investigation also revealed that the serum IL-10 level was positively related to the serum sFasL level.…”

sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease

“…Serum sFasL supplementation may help prevent damage to glandular organs in Sjögren’s syndrome, which was demonstrated to be associated with decreased levels of sFasL in blood [ 99 ]. On the other hand, ex vivo depletion of sFasL was efficient in depleting alloreacting human donor anti-host T-cells in graft-versus-host disease [ 100 ].…”