Interleukin-28A promotes IFN-γ production by peripheral blood mononuclear cells from patients with Behçet’s disease
Introduction
Three highly related cytokines IL-28A (IFN-λ2), IL-28B (IFN-λ3) and IL-29 (IFN-λ1) were discovered in 2003. These cytokines signal through a heterodimeric receptor consisting of IL-28Ra (IFN-lR1 or CRF2-12) responsible for ligand specificity and IL-10Rb (IL-10R2 or CRF2-4) shared with all other IL-10 family members [1], [2], [3]. The potent antiviral and anti-cancer activities of IFN-λs are well established [4], [5], [6]. More recently, immunoregulatory functions of IFN-λs have also been suggested. These activities include increasing NK and T cell cytotoxicity [6], upregulating MHC class I molecule expression on tumor cells to promote antigen presentation [1], [2] and mediating cell apoptosis [7], [8], [9]. More interestingly, transgenic expression of IL-28A in vivo promotes the induction of Th1 responses and the severity of Concanavalin (ConA)-induced liver injury [10]. These data suggest that IL-28A functions as a key mediator in immune responses.
Behçet’s disease (BD) is a chronic systemic inflammatory autoimmune disease of unknown etiology. It is characterized by recurrent episodes of oral and genital ulcers, uveitis, and cutaneous, vascular, and neurological involvement [11], [12]. It is one of the most common forms of uveitis in China and Japan [13]. A number of clinical and laboratory findings suggest a strong polarized Th1 and Th17 immune response in BD and in experimental autoimmune uveoretinitis (EAU), a model of human uveitis induced by immunization with retinal antigen interphotoreceptor retinoid-binding protein (IRBP) [14], [15], [16], [17], [18]. As yet, it is not clear whether IL-28A is involved in BD development. In view of the role of IL-28A in autoimmune diseases, the present study was designed to examine the capacity of IL-28A to induce the production of IFN-γ and IL-17 by peripheral blood mononuclear cells (PBMCs) from BD patients.
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Patients
Nineteen BD patients with active uveitis (10 men and 9 women; mean age, 41 years; range, 20–56 years) referred to Zhongshan Ophthalmic Center, Sun Yat-sen University in Guangzhou, PR China, were included in this study. The diagnosis of Behçet’s disease was based on the criteria designed by the International Study Group for Behçet’s disease [19]. All patients, referred from various provinces throughout China, showed a recurrent intraocular inflammation (active uveitis stage). These patients had
Levels of IFN-γ, Il-4 and IL-17 in the sera from BD patients and control subjects
The levels of IFN-γ, IL-4 and IL-17 in the sera from BD patients and control subjects were measured by ELISA. The sensitivity detection of IFN-γ, IL-17, and IL-4 was 15.625 pg/ml, 15.625 pg/ml and 31.25 pg/ml, respectively. The levels of IFN-γ, IL-4 and IL-17 in the sera were undetectable (data not shown).
The effects of IL-28A on the expression of IFN-γ and IL-17 mRNA by PBMCs from BD patients and normal subjects
The levels of IFN-γ and IL-17 mRNA in PBMCs from BD patients and normal subjects were determined by qRT-PCR. A polyclonal stimulant PHA, increased the expression of IFN-γ mRNA by PBMCs from both
Discussion
Although the potent antiviral and antitumor functions of IL-28A are well established [20], [21], [22], less attention has been paid to the activities of IL-28A on PBMCs from patients. In the present study, we found that IL-28A significantly increased the expression of IFN-γ at both the mRNA and protein levels by PHA-stimulated PBMCs from BD patients compared with PBMCs from control subjects. These results suggest that BD patient PBMCs are highly sensitive to IL-28A which may promote Th1
Contributors
B.L., C.X., X.L. and S.B.S. made substantial contributions to conception and design, acquisition of data, analysis and interpretation of data. B.L. and S.B.S. were in drafting the article and revising it critically for important intellectual content and final approval of the version to be published.
Ethics approval
Ethics committee at Zhongshan Ophthalmic Center, Sun Yat-sen University, China.
Acknowledgments
We are grateful to Hongyan Zhou and Xiangkun Huang for their technical assistance. This work was supported by grants from the Science and Technology Planning Project of Guangdong Province, China (2009B030801170), and the Fundamental Research Funds of State Key Laboratory of Ophthalmology (303060202400439).
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