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

Hoshino, Akihiro; Nagao, Tomokazu; Nagi-Miura, Noriko; Ohno, Naohito; Yasuhara, Masato; Yamamoto, Kenji; Nakayama, Toshinori; Suzuki, Kazuo

doi:10.1016/j.jaut.2008.03.006

Cited by 95 publications

(63 citation statements)

References 58 publications

(73 reference statements)

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“…1H) if surface ligand-receptor complexes were internalized; 2) the expectation that receptor-mediated internalization would result in clearance rather than intracellular accumulation of the ligand (14,28); and 3) the evidence that neutrophils can actively release IL-17, as provided by our human data (Fig. 6E) and by previous mouse studies (10,16,22,24,34,41).…”

Section: Discussionmentioning

confidence: 79%

“…Moreover, murine neutrophils have been shown to release IL-17 in vitro upon stimulation with anti-MPO antibodies (16). Since IL-17 knockout mice were largely protected from anti-MPO glomerulonephritis (15), it is tempting to speculate whether the pathogenesis of this ANCA-GN-like model may depend on the release of IL-17 from anti-MPO antibody-activated neutrophils.…”

Section: Discussionmentioning

confidence: 99%

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Renal IL-17 expression in human ANCA-associated glomerulonephritis

Velden

Paust

Hoxha

et al. 2012

American Journal of Physiology-Renal Physiology

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Interleukin-17A (IL-17) promotes inflammatory renal tissue damage in mouse models of crescentic glomerulonephritis, including murine experimental autoimmune anti-myeloperoxidase glomerulonephritis, which most likely depends on IL-17-producing Th17 cells. In human anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, however, the cellular sources of IL-17 remain to be elucidated. Therefore, we analyzed human kidney biopsies of active necrotizing and crescentic ANCA-associated glomerulonephritis by immunohistochemistry using an IL-17-specific antibody and by immunofluorescent colocalization with cell type markers. We detected numerous IL-17-expressing (IL-17+) cells in the glomeruli and in the tubulointerstitium. Unexpectedly, most of these IL-17+ cells were polymorphonuclear neutrophilic granulocytes, while IL-17+ T cells and IL-17+ mast cells were present at significantly lower frequencies. IL-17 was not detected in other infiltrating or resident kidney cells. In those patients who had not received immunosuppressive treatment before biopsy, serum creatinine levels were positively correlated with tubulointerstitial IL-17+ neutrophils as well as IL-17+ T cells. Furthermore, we could demonstrate that purified human blood neutrophils expressed IL-17 protein and released it upon stimulation in vitro. In conclusion, these results support a pathogenic role for IL-17 in human ANCA-associated glomerulonephritis. Our data suggest that in the acute stage of the disease neutrophils may act as an important immediate-early innate source of IL-17 and may thereby initiate and promote ongoing renal inflammation. IL-17 may thus be a target for treating acute ANCA-associated glomerulonephritis.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Renal IL-17 expression in human ANCA-associated glomerulonephritis

Velden

Paust

Hoxha

et al. 2012

American Journal of Physiology-Renal Physiology

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“…A previous study with a model of lung neutrophilia induced by LPS instillation reported the detection of IL-17 mRNA in neutrophils (13). Subsequently, it was shown that IL-17 can be produced by non-T cells during "sterile" inflammation of the kidneys (30) and in a model of acute vasculitis (23). Intriguingly, in a model of Helicobacter hepaticus-induced colitis, Gr-1 ϩ CD11b ϩ cells produced a significant amount of IL-17 in the gut lamina propria (24).…”

Section: Discussionmentioning

confidence: 99%

“…In the lung, besides the classical Th17 lineage, innate cells such as ␥␦ T and NKT cells produce IL-17 during infection, sparking a quick start to the immune response. Recent reports suggest that neutrophils may also be a novel player in the game, as shown in noninfectious inflammation models such as acute ischemia-reperfusion in the kidney (30), lung lipopolysaccharide (LPS)-induced neutrophilia (13), and acute vasculitis (23). More recently, neutrophils have been shown to produce IL-17A in the lung after fungal infection by Cryptococcus neoformans (55) and Aspergillus fumigatus (54).…”

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confidence: 99%

Differential Role of the Interleukin-17 Axis and Neutrophils in Resolution of Inhalational Anthrax

et al. 2012

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The roles of interleukin-17 (IL-17) and neutrophils in the lung have been described as those of two intricate but independent players. Here we identify neutrophils as the primary IL-17-secreting subset of cells in a model of inhalation anthrax using A/J and C57BL/6 mice. With IL-17 receptor A knockout (IL-17RA ؊/؊ ) mice, we confirmed that IL-17A/F signaling is instrumental in the self-recruitment of this population. We also show that the IL-17A/F axis is critical for surviving pulmonary infection, as IL-17RA ؊/؊ mice become susceptible to intranasal infection by Bacillus anthracis Sterne spores. Strikingly, infection with a fully virulent strain did not affect IL-17RA ؊/؊ mouse survival. Eventually, by depleting neutrophils in wild-type and IL-17RA ؊/؊ mice, we demonstrated the crucial role of IL-17-secreting neutrophils in mouse survival of infection by fully virulent B. anthracis. This work demonstrates the important roles of both IL-17 signaling and neutrophils in clearing this pathogen and surviving pulmonary B. anthracis infection.

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“…Several studies have provided evidence that neutrophils can express IL-17A either at the protein level using immunohistochemistry or flow cytometry (19,26) or at the mRNA level using real-time PCR (42,43). However, it has been shown that the IL-17A receptor (IL-17RA) is ubiquitously expressed, including neutrophils, and that abundant expression of IL-17RA could allow neutrophils to avidly bind IL-17A secreted by other cells (29,44,45).…”

Section: Discussionmentioning

confidence: 99%

Natural Killer T Cell–derived IL-17 Mediates Lung Ischemia–Reperfusion Injury

Sharma¹,

LaPar²,

Zhao³

et al. 2011

Am J Respir Crit Care Med

107

133

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Rationale: We recently implicated a role for CD4 1 T cells and demonstrated elevated IL-17A expression in lung ischemia-reperfusion (IR) injury. However, identification of the specific subset of CD4 1 T cells and their mechanistic role in IR injury remains unknown. Objectives: We tested the hypothesis that invariant natural killer T (iNKT) cells mediate lung IR injury via IL-17A signaling. Methods: Mice underwent lung IR via left hilar ligation. Pulmonary function was measured using an isolated lung system. Lung injury was assessed by measuring edema (wet/dry weight) and vascular permeability (Evans blue dye). Inflammation was assessed by measuring proinflammatory cytokines in lungs, and neutrophil infiltration was measured by immunohistochemistry and myeloperoxidase levels. Measurements and Main Results: Pulmonary dysfunction (increased airway resistance and pulmonary artery pressure and decreased pulmonary compliance), injury (edema, vascular permeability), and inflammation (elevated IL-17A; IL-6; tumor necrosis factor-a; monocyte chemotactic protein-1; keratinocyte-derived chemokine; regulated upon activation, normal T-cell expressed and secreted; and neutrophil infiltration) after IR were attenuated in IL-17A 2/2 and Rag-1 2/2 mice. Anti-IL-17A antibody attenuated lung dysfunction in wildtype mice after IR. Reconstitution of Rag-1 2/2 mice with wild-type, but not IL-17A 2/2 , CD4 1 T cells restored lung dysfunction, injury, and inflammation after IR. Lung dysfunction, injury, IL-17A expression, and neutrophil infiltration were attenuated in Ja18 2/2 mice after IR, all of which were restored by reconstitution with wild-type, but not IL-17A 2/2 , iNKT cells. Flow cytometry and enzyme-linked immunosorbent spot assay confirmed IL-17A production by iNKT cells after IR.Conclusions: These results demonstrate that CD4 1 iNKT cells play a pivotal role in initiating lung injury, inflammation, and neutrophil recruitment after IR via an IL-17A-dependent mechanism.

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

Cited by 95 publications

References 58 publications

Renal IL-17 expression in human ANCA-associated glomerulonephritis

Renal IL-17 expression in human ANCA-associated glomerulonephritis

Differential Role of the Interleukin-17 Axis and Neutrophils in Resolution of Inhalational Anthrax

Natural Killer T Cell–derived IL-17 Mediates Lung Ischemia–Reperfusion Injury

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