IgA Triggers Cell Death of Neutrophils When Primed by Inflammatory Mediators

IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists....

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Published in:The Journal of immunology (1950) 2020-11, Vol.205 (10), p.2640-2648
Main Authors: Wehrli, Marc, Schneider, Christoph, Cortinas-Elizondo, Fabiola, Verschoor, Daniëlle, Frias Boligan, Kayluz, Adams, Olivia Joan, Hlushchuk, Ruslan, Engelmann, Christine, Daudel, Fritz, Villiger, Peter M, Seibold, Frank, Yawalkar, Nikhil, Vonarburg, Cédric, Miescher, Sylvia, Lötscher, Marius, Kaufmann, Thomas, Münz, Christian, Mueller, Christoph, Djonov, Valentin, Simon, Hans-Uwe, von Gunten, Stephan
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Apoptosis - immunology
Arthritis, Rheumatoid - blood
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - immunology
Cell Survival - drug effects
Cell Survival - immunology
Cells, Cultured
Coculture Techniques
Crohn Disease - blood
Crohn Disease - drug therapy
Crohn Disease - immunology
Humans
Immunoglobulin A - pharmacology
Immunoglobulin A - therapeutic use
Immunoglobulins, Intravenous - pharmacology
Immunoglobulins, Intravenous - therapeutic use
Macrophages
Mice
Neutrophils - drug effects
Neutrophils - immunology
Primary Cell Culture
Sepsis - blood
Sepsis - drug therapy
Sepsis - immunology
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Summary:IVIG preparations consisting of pooled IgG are increasingly used for the treatment of autoimmune diseases. IVIG is known to regulate the viability of immune cells, including neutrophils. We report that plasma-derived IgA efficiently triggers death of neutrophils primed by cytokines or TLR agonists. IgA-mediated programmed neutrophil death was PI3K-, p38 MAPK-, and JNK-dependent and evoked anti-inflammatory cytokines in macrophage cocultures. Neutrophils from patients with acute Crohn's disease, rheumatoid arthritis, or sepsis were susceptible to both IgA- and IVIG-mediated death. In contrast to IVIG, IgA did not promote cell death of quiescent neutrophils. Our findings suggest that plasma-derived IgA might provide a therapeutic option for the treatment of neutrophil-associated inflammatory disorders.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1900883