Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity

Qian Wu,Hongsheng Sun,Yuanchao Zhang,Qingrui Yang,Elaine Lourenco

doi:10.1186/ar3363

Abstract

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Previous studies have suggested that interferon-lambda 1 (IFN-λ1), a type III interferon, plays an immunomodulatory role. In this study we investigated its role in SLE, including its correlation with disease activity, organ disorder and production of chemokines.MethodsWe determined levels of IFN-λ1 mRNA in peripheral blood mononuclear cells (PBMC) and serum protein levels in patients with SLE using real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunoassay (ELISA). Further, we detected the concentration of IFN-inducible protein-10 (IP-10), monokine induced by IFN-γ (MIG) and interleukin-8 (IL-8) secreted by PBMC under the stimulation of IFN-λ1 using ELISA.ResultsIFN-λ1 mRNA and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IFN-λ1 mRNA and serum protein levels compared with those with inactive disease as well. Serum IFN-λ1 levels were positively correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), anti-dsDNA antibody, C-reactive protein (CRP) and negatively correlated with complement 3. Serum IFN-λ1 levels were higher in SLE patients with renal involvement and arthritis compared with patients without the above-mentioned manifestations. IFN-λ1 with different concentrations displayed different effects on the secretion of the chemokines IP-10, MIG and IL-8.ConclusionsThese findings indicate that IFN-λ1 is probably involved in the renal disorder and arthritis progression of SLE and associated with disease activity. Moreover, it probably plays an important role in the pathogenesis of SLE by stimulating secretion of the chemokines IP-10, MIG and IL-8. Thus, IFN-λ1 may provide a novel research target for the pathogenesis and therapy of SLE.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems
interferon-lambda 1 (IFN-l1) mRNA and serum protein levels were higher in patients with SLE compared with healthy controls Initially, the expression of IFN-l1 mRNA in peripheral blood mononuclear cells (PBMC) and serum IFN-l1 protein levels from 42 SLE patients and 25 normal controls (NC) were measured using real-time reverse transcription polymerase chain reaction (PCR) and enzyme-linked immunoassay (ELISA), respectively
IFN-l1 mRNA and serum protein levels were higher in SLE patients with active disease compared with those with inactive disease We investigated whether IFN-l1 was related to disease activity in SLE patients

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease characterized by the activation of T and polyclonal B lymphocytes, production of numerous autoantibodies, and formation of immune complexes that result in tissue and organ damage [1]. Type III IFN, IFN-l1, IFN-l2, IFN-l3, referred to as interleukin (IL)-29, IL-28A and IL-28B, respectively, are novel members of the IFN super-family [7,8] They are secreted by human peripheral blood mononuclear cells (PBMC) as well as dendritic cells (DC) upon infection with viruses or stimulation with poly (I:C) or lipopolysaccharide (LPS) [2,8], and express in a broad spectrum of tissues [7]. Gene expressions are regulated by virus-activated interferon regulatory factor (IRF) 3 and IRF 7 [9] These proteins induce activation of JAK/STAT signaling pathways through a cell-surface receptor consisting of two chains, IFN-lR1, which is IFN-l- specific, and IL-10R2, which is shared among IL-10, IL-22 and IL-26 [10,11]. IFN-l1 was able to inhibit human type 2 helper T (Th2) cell responses by diminishing secretion of IL-13, and upregulated cytokines IL-6, IL-8 and IL-10 levels secreted by monocytes in a dose-dependent manner [17-19]

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