Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjögren's syndrome

Keiko Yoshimoto,Katsuya Suzuki,Tohru Abe,Tsutomu Takeuchi,Masako Kojima,Yoko Ogawa,Maiko Tanaka,Kazuo Tsubota,Kensei Tsuzaka,Yumiko Setoyama,Hideto Kameda

doi:10.1186/ar3493

Abstract

IntroductionIn this study, we investigated possible aberrations of monocytes from patients with primary Sjögren's syndrome (pSS). We focused on B-cell-activating factor of the TNF family (BAFF) and IL-6 because they are both produced by monocytes and are known to be involved in the pathogenesis of pSS.MethodsPeripheral monocytes were prepared from both pSS patients and normal individuals. The cells were stimulated in vitro with IFN-γ, and the amounts of IL-6 and soluble BAFF (sBAFF) produced by the cells were quantitated. The effect of sBAFF itself on the production of IL-6 was also studied. To investigate the response of pSS monocytes to these stimuli, the expression levels of the genes encoding BAFF receptors and IL-6-regulating transcription factors were quantitated.ResultsPeripheral pSS monocytes produced significantly higher amounts of sBAFF and IL-6 than normal monocytes did, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-γ. The elevated production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of pSS monocytes with sBAFF induced a significant increase in IL-6 production. Moreover, the expression levels of a BAFF receptor and transcription factors regulating IL-6 were significantly elevated in pSS monocytes compared to normal monocytes.ConclusionsThe results of the present study suggest that the mechanisms underlying the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is due to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may cause the development of pSS.

Highlights

In this study, we investigated possible aberrations of monocytes from patients with primary Sjögren’s syndrome
Aberrant production of soluble B-cell-activating factor of the TNF family (BAFF) (sBAFF) by primary Sjögren’s syndrome (pSS) monocytes Peripheral monocytes were prepared from primary pSS patients and normal individuals
Aberrant expression of BAFF receptors in pSS monocytes it has been reported that BAFF receptors are mainly expressed in lymphocytes [37], our results suggest that BAFF receptors are expressed in monocytes

Summary

Introduction

We investigated possible aberrations of monocytes from patients with primary Sjögren’s syndrome (pSS). B-cell-activating factor of the TNF family (BAFF) (tumor necrosis factor ligand superfamily, member 13b) is a cytokine which is primarily produced by monocytes and dendritic cells [2,3,4] in addition to T cells [5,6]. It plays a crucial role in the proliferation, differentiation and survival of B cells [2,4,5,7]. Elevated production of BAFF has been linked to the development of another autoimmune disease, systemic lupus erythematosus [24,25,26]

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Conclusion