MPO-ANCA induces IL-17 production by activated neutrophils in vitro via its Fc region- and complement-dependent manner

• Published in: Journal of autoimmunity Vol. 31; no. 1; pp. 79 - 89
• Main Authors: Hoshino, Akiyoshi, Nagao, Tomokazu, Nagi-Miura, Noriko, Ohno, Naohito, Yasuhara, Masato, Yamamoto, Kenji, Nakayama, Toshinori, Suzuki, Kazuo
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.08.2008
• Subjects: Allergy and Immunology; ANCA; Autoantibodies; Autoimmunity; Candida albicans; Chemokine; Complement; Coronary arteritis; Crescentic glomerulonephritis; Cytokine; Fungal infection; IL-17A; IL-23; Inflammation; Mannoprotein; Myeloperoxidase; Neutrophils; Vasculitis; β-Glucan; Autoimmunity; Candida albicans; pertussis toxin from Bordetella pertussis; Ab; Crescentic glomerulonephritis; Complement; IL-23; MPO; Coronary arteritis; Vasculitis; MPO-specific anti-neutrophil cytoplasmic autoantibody; ANCA; PTX; C. albicans water-soluble mannoprotein and β-glucan complex; Myeloperoxidase; β-Glucan; Autoantibodies; antibody; anti-neutrophil cytoplasmic antibody; IL-17A; CAWS; H&E; Cytokine; Neutrophils; Inflammation; Mannoprotein; Chemokine; hematoxylin/eosin; G-protein coupled receptor(s); MPO-ANCA; GPCR; Fungal infection; myeloperoxidase(s)
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2008.03.006

Abstract The elevation of serum anti-neutrophil cytoplasmic autoantibodies (ANCA) is significantly associated with the progression of some patients with systemic vasculitis. Especially, myeloperoxidase-specific ANCA (MPO-ANCA) play a pivotal role in the progression of systemic vasculitis including crescentic glomerulonephritis. Here we demonstrated that MPO-ANCA-activated neutrophils allow the local environment to differentiate Th17 cells through IL-6, IL-17A, and IL-23 production. We found a variety of elevated serum cytokines, especially IL-17A, in ANCA-mediated systemic vasculitis mice. Furthermore, activated peritoneal neutrophils in vitro also produced IL-17A and IL-23 in response to MPO-ANCA. Co-stimulation of fungal mannoprotein and complements significantly enhanced the MPO-ANCA-mediated IL-17A expression, but F( ab )′2 fragments of MPO-ANCA diminished the cytokine response. These results suggest that the activated neutrophils produce IL-17A and IL-23 in response to MPO-ANCA via their Fc-region and classical complement pathway, which initiate the first steps of chronic autoimmune inflammation by allowing the local environment to develop Th17 -mediated autoimmunity.