Abstract
ObjectiveInterleukin (IL)-22 has been reported to be involved in the development of autoimmune diseases. This study aimed to analyze the expression and potential role of IL-22 in the pathogenesis of Behcet’s disease (BD).MethodsThe levels of IL-22 in patient sera or supernatants of cultured peripheral blood mononuclear cells (PBMCs) and CD4+T cells were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to evaluate the frequency of IL-22–producing CD4+ T cells. IL-22 mRNA from erythema nodosum skin lesions was examined using real time quantitative RT-PCR.ResultsBD patients with active uveitis showed a significantly higher expression of IL-22 in the supernatants of stimulated PBMCs and CD4+T cells compared with BD patients without active uveitis and normal controls. An increased frequency of IL-22-producing CD4+T cells was also found in BD patients with active uveitis. IL-22 mRNA expression was elevated in erythema nodosum skin lesions. In BD patients, a high IL-22 level in the supernatant of stimulated PBMCs correlated with the presence of retinal vasculitis and erythema nodosum.ConclusionsIL-22 was associated with disease activity in BD and correlated with the presence of small vessel inflammation, suggesting that it may be involved in its pathogenesis.
Highlights
Our results showed that IL-22 was associated with the activity of Behcet’s disease (BD) and the occurrence of small vessel inflammation, suggesting it may be involved in its pathogenesis
Increased Expression of IL-22 in the Supernatants of Stimulated peripheral blood mononuclear cells (PBMCs) and CD4+ T Cells from BD Patients with Active Uveitis There was no significant difference with regards to IL-22 serum levels among BD patients with active uveitis (1536106 pg/ml, n = 18), BD patients without active uveitis (93671 pg/ml, n = 17), acute anterior uveitis (AAU) patients (128679 pg/ml, n = 12) or normal controls (113695 pg/ml, n = 18) (Fig. 1C)
After stimulation with anti-CD3 and anti-CD28 antibodies, a considerably higher concentration of IL-22 could be detected in PBMCs from BD patients with active uveitis (13826489 pg/ml) compared to that observed in BD patients without active uveitis (7786211 pg/ml, p,0.001), AAU patients (9116271 pg/ml, p = 0.011) or normal controls (8866190 pg/ml, p = 0.004) (Fig. 1A)
Summary
Interleukin (IL)-22, a member of the IL-10 superfamily, is primarily produced by activated T cells and natural killer (NK) cells. [1,2] It is often secreted together with IL-17 by Th17 cells. [3,4] IL-22 mediates its effect through 2 receptors: IL-10Rb, which is ubiquitously expressed and the heterodimeric receptor IL22R1, which is restricted to nonlymphoid cells such as epithelial cells and fibroblasts. [2,5] Upon binding to its receptor, IL-22 can initiate inflammatory immune responses and has been shown to induce production of CCL-2 and proliferation of synovial fibroblasts and osteoclasts in rheumatoid arthritis (RA). [6,7] Recent studies have shown that IL-22 may be involved in the pathogenesis of autoimmune diseases including psoriasis, Crohns disease (CD), rheumatoid arthritis (RA), Sjogren’s syndrome and systemic lupus erythematosus (SLE). [8,9,10,11,12] Earlier studies showed that IL-22 mRNA was highly expressed by PBMCs from noninfectious uveitis patients [13].IL-22 is involved in the survival of cells in the liver, lungs and gut and may have a protective effect besides its proinflammatory activity.[14,15,16] It has for instance been shown to be protective against experimental hepatitis and Crohns disease (CD) [17].Behcet’s disease (BD) is a chronic systemic inflammatory disease characterized by recurrent uveitis, oral aphthae, genital ulcers, and skin lesions. [6,7] Recent studies have shown that IL-22 may be involved in the pathogenesis of autoimmune diseases including psoriasis, Crohns disease (CD), rheumatoid arthritis (RA), Sjogren’s syndrome and systemic lupus erythematosus (SLE). IL-22 is involved in the survival of cells in the liver, lungs and gut and may have a protective effect besides its proinflammatory activity.[14,15,16] It has for instance been shown to be protective against experimental hepatitis and Crohns disease (CD) [17]. Recent studies from our group have suggested that Th17 plays an active role in this disease. Our results showed that IL-22 was associated with the activity of BD and the occurrence of small vessel inflammation, suggesting it may be involved in its pathogenesis
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