MPO-ANCA induces IL-17 production by activated neutrophils in vitro via classical complement pathway-dependent manner

作者：Hoshino Akiyoshi; Nagao Tomokazu; Nagi Miura Noriko; Ohno Naohito; Yasuhara Masato; Yamamoto Kenji; Nakayama Toshinori; Suzuki Kazuo^*

来源：Journal of Autoimmunity, 2008, 31(1): 79-89.

DOI：10.1016/j.jaut.2008.03.006

• ANCA
• autoantibodies
• autoimmunity
• beta-glucan
• Candida albicans
• chemokine
• complement
• coronary arteritis
• crescentic glomerulonephritis
• cytokine
• fungal infection
• inflammation
• IL-17A
• IL-23
• mannoprotein
• myeloperoxidase
• neutrophils
• vasculitis

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 Th-17 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 classical complement pathway, which initiate the first steps of chronic autoimmune inflammation by allowing the local environment to develop Th-17-mediated autoimmunity.

• 出版日期2008-8