IL-4 receptor engagement in human neutrophils impairs their migration and extracellular trap formation.

The Journal of Allergy and Clinical Immunology
Daniela ImpellizzieriOnur Boyman

Abstract

Type 2 immunity serves to resist parasitic helminths, venoms, and toxins, but the role and regulation of neutrophils during type 2 immune responses are controversial. Helminth models suggested a contribution of neutrophils to type 2 immunity, whereas neutrophils are associated with increased disease severity during type 2 inflammatory disorders, such as asthma. We sought to evaluate the effect of the prototypic type 2 cytokines IL-4 and IL-13 on human neutrophils. Human neutrophils from peripheral blood were assessed without or with IL-4 or IL-13 for (1) expression of IL-4 receptor subunits, (2) neutrophil extracellular trap (NET) formation, (3) migration toward CXCL8 in vitro and in humanized mice, and (4) CXCR1, CXCR2, and CXCR4 expression, as well as (5) in nonallergic versus allergic subjects. Human neutrophils expressed both types of IL-4 receptors, and their stimulation through IL-4 or IL-13 diminished their ability to form NETs and migrate toward CXCL8 in vitro. Likewise, in vivo chemotaxis in NOD-scid-Il2rg-/- mice was reduced in IL-4-stimulated human neutrophils compared with control values. These effects were accompanied by downregulation of the CXCL8-binding chemokine receptors CXCR1 and CXCR2 on human neutrophils on...Continue Reading

Citations

Oct 9, 2019·Allergy·Thomas EiweggerJulia Upton
Apr 3, 2020·Cellular & Molecular Immunology·Mieke MetzemaekersPaul Proost
Jun 25, 2020·Clinical and Experimental Immunology·T NovakE Hagi-Pavli
Sep 22, 2020·PLoS Pathogens·Bridget KastelbergShiv D Kale
Jan 26, 2020·Proceedings of the National Academy of Sciences of the United States of America·Sudeepta Kumar PandaFredrik Wermeling
Oct 28, 2019·Cellular and Molecular Life Sciences : CMLS·Aneta Manda-HandzlikUrszula Demkow
Oct 28, 2020·Antioxidants & Redox Signaling·Christian SchulzHellen Ishikawa-Ankerhold
Jun 12, 2020·The Journal of Allergy and Clinical Immunology·John W SteinkeLarry Borish
Dec 23, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Di WuZhengkai Wei
Dec 24, 2020·Nature Communications·Dilara SahinOnur Boyman
Feb 2, 2021·Cell Reports Medicine·Stéphane ChevrierBernd Bodenmiller

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