IgA triggers cell death of neutrophils when primed by inflammatory mediators

Marc Wehrli; Christoph Schneider; Fabiola Cortinas-Elizondo; Danielle Verschoor; Kayluz Frias Boligan; Olivia Joan Adams; Ruslan Hlushchuk; Christine Engelmann; Fritz Daudel; Peter M. Villiger; Frank Seibold; Nikhil Yawalkar; Cedric Vonarburg; Sylvia Miescher; Marius Lotscher; Thomas Kaufmann; Christian Munz; Christoph Mueller; Valentin Djonov; Hans Uwe Simon; Stephan Von Gunten

doi:10.4049/jimmunol.1900883

IgA triggers cell death of neutrophils when primed by inflammatory mediators

Marc Wehrli, Christoph Schneider, Fabiola Cortinas-Elizondo, Danielle Verschoor, Kayluz Frias Boligan, Olivia Joan Adams, Ruslan Hlushchuk, Christine Engelmann, Fritz Daudel, Peter M. Villiger, Frank Seibold, Nikhil Yawalkar, Cedric Vonarburg, Sylvia Miescher, Marius Lotscher, Thomas Kaufmann, Christian Munz, Christoph Mueller, Valentin Djonov, Hans Uwe SimonStephan Von Gunten

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

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 JNKdependent 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.

Original language	English
Pages (from-to)	2640-2648
Number of pages	9
Journal	Journal of Immunology
Volume	205
Issue number	10
DOIs	https://doi.org/10.4049/jimmunol.1900883
State	Published - 15 Nov 2020
Externally published	Yes

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Wehrli, M., Schneider, C., Cortinas-Elizondo, F., Verschoor, D., Boligan, K. F., Adams, O. J., Hlushchuk, R., Engelmann, C., Daudel, F., Villiger, P. M., Seibold, F., Yawalkar, N., Vonarburg, C., Miescher, S., Lotscher, M., Kaufmann, T., Munz, C., Mueller, C., Djonov, V., ... Gunten, S. V. (2020). IgA triggers cell death of neutrophils when primed by inflammatory mediators. Journal of Immunology, 205(10), 2640-2648. https://doi.org/10.4049/jimmunol.1900883

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title = "IgA triggers cell death of neutrophils when primed by inflammatory mediators",

abstract = "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 JNKdependent 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.",

author = "Marc Wehrli and Christoph Schneider and Fabiola Cortinas-Elizondo and Danielle Verschoor and Boligan, {Kayluz Frias} and Adams, {Olivia Joan} and Ruslan Hlushchuk and Christine Engelmann and Fritz Daudel and Villiger, {Peter M.} and Frank Seibold and Nikhil Yawalkar and Cedric Vonarburg and Sylvia Miescher and Marius Lotscher and Thomas Kaufmann and Christian Munz and Christoph Mueller and Valentin Djonov and Simon, {Hans Uwe} and Gunten, {Stephan Von}",

year = "2020",

month = nov,

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doi = "10.4049/jimmunol.1900883",

language = "English",

volume = "205",

pages = "2640--2648",

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Wehrli, M, Schneider, C, Cortinas-Elizondo, F, Verschoor, D, Boligan, KF, Adams, OJ, Hlushchuk, R, Engelmann, C, Daudel, F, Villiger, PM, Seibold, F, Yawalkar, N, Vonarburg, C, Miescher, S, Lotscher, M, Kaufmann, T, Munz, C, Mueller, C, Djonov, V, Simon, HU & Gunten, SV 2020, 'IgA triggers cell death of neutrophils when primed by inflammatory mediators', Journal of Immunology, vol. 205, no. 10, pp. 2640-2648. https://doi.org/10.4049/jimmunol.1900883

TY - JOUR

T1 - IgA triggers cell death of neutrophils when primed by inflammatory mediators

AU - Wehrli, Marc

AU - Schneider, Christoph

AU - Cortinas-Elizondo, Fabiola

AU - Verschoor, Danielle

AU - Boligan, Kayluz Frias

AU - Adams, Olivia Joan

AU - Hlushchuk, Ruslan

AU - Engelmann, Christine

AU - Daudel, Fritz

AU - Villiger, Peter M.

AU - Seibold, Frank

AU - Yawalkar, Nikhil

AU - Vonarburg, Cedric

AU - Miescher, Sylvia

AU - Lotscher, Marius

AU - Kaufmann, Thomas

AU - Munz, Christian

AU - Mueller, Christoph

AU - Djonov, Valentin

AU - Simon, Hans Uwe

AU - Gunten, Stephan Von

PY - 2020/11/15

Y1 - 2020/11/15

N2 - 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 JNKdependent 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.

AB - 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 JNKdependent 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.

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SN - 0022-1767

VL - 205

SP - 2640

EP - 2648

JO - Journal of Immunology

JF - Journal of Immunology

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ER -

IgA triggers cell death of neutrophils when primed by inflammatory mediators

Abstract

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