Patients with non-relapsing ANCA-associated vasculitis have increased numbers of circulating IL-10 producing Th17 cells
© Cohen Tervaert et al; licensee BioMed Central Ltd. 2010
Published: 25 November 2010
IL-17 producing T-cells (Th17) were recently defined as a new, pro-inflammatory T-cell subset and are considered to have a key role in autoimmune diseases.
Importantly, it was recently described that anti-inflammatory regulatory T-cells (Treg) are able to convert to pro-inflammatory Th17 cells (“Plasticity”) and vice versa. Little is known about the Th17 response or plasticity in ANCA-associated vasculitis (AAV). Therefore, we investigated Th17 responses in AAV.
Patients and methods
47 patients with ANCA-associated vasculitis and 12 age-matched healthy controls (HC) were studied. PBMC were isolated by ficoll gradient centrifugation and stimulated for 4 hours with phorbol-myristate-acetate/ionomycin in presence of brefeldin A. Intracellular staining was performed to detect IFNg, IL-4, IL-10 and IL-17A producing T-helper-cells by flow cytometry. Ten renal biopsies with necrotizing-crescentic-glomerulonephritis (NCGN) were stained for IL-17 by immunohistochemistry.
AAV patients in remission (n=27) and with active disease (n=20) had increased numbers of circulating IL-17A+ T-helper-cells as compared to HC (2.04 ±1.65% vs. 0.73 ±0,36%, p<0.0005 and 1.85 ±2.15% vs. 0.73 ±0,36%, p=0.05). Lesional IL-17+ cells were present in renal biopsies with necrotizing crescentic glomerulonephritis (NCGN). Moreover, IL-10+/IL-17+ T-helper-cells were found both in HC and AAV patients. However, AAV patients showed higher numbers of IL-10+/IL-17+ T-helper-cells than HC (0.054 ±0.048% vs. 0.025 ±0.014%, p<0.05). Furthermore, patients with non-relapsing disease course had significantly more IL-10 producing cells Th17 cells than patients with relapsing disease course (0.063 ±0.039% vs. 0.041 ±0.056%, p<0.05).
The results of this study emphasize the importance of circulating and lesional Th17 cells in AAV. IL-17+ cells participate in renal inflammation related to AAV. Elevated numbers of IL-10 producing Th17-cells are demonstrated for the first time in AAV and might point at enhanced plasticity. Further efforts are needed to unravel the role of Th17 cells in AAV.
This article is published under license to BioMed Central Ltd.