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Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils


Heeb, Lukas E M; Egholm, Cecilie; Boyman, Onur (2020). Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils. Genes and immunity, 21(3):143-149.

Abstract

The cytokines interleukin (IL)-4 and IL-13, signaling via the IL-4 receptor (IL-4R), orchestrate type 2 immunity to helminth infections and toxins. Activation of epithelial and myeloid cells, and a transient neutrophils influx initiates type 2 immune responses, which are dominated by basophils, eosinophils, mast cells, B cell immunoglobulin E production, and type 2 T helper and T follicular helper cells. Interestingly, IL-4 and IL-13 can curtail chemotaxis and several effector functions of neutrophils in mice and humans. This inhibitory role of IL-4 and IL-13 probably developed to limit tissue damage by neutrophils during type 2 immunity where a “weep and sweep” response aims at expulsion and decreased fecundity, instead of killing, of macroparasites. Here, we review when IL-4R signaling cytokines appeared during evolution relative to neutrophils and adaptive immunity. Neutrophil-like granular phagocytes were present in invertebrates throughout the bilaterian clade, but we were unable to find data on IL-4, IL-13, or their receptors in invertebrates. Conversely, vertebrates had both adaptive immunity and IL-4, IL-13, and IL-4Rs, suggesting that type 2 cytokines evolved together with adaptive immunity. Further studies are necessary to determine whether IL-4R signaling in neutrophils was established simultaneously with the appearance of adaptive immunity or later.

Abstract

The cytokines interleukin (IL)-4 and IL-13, signaling via the IL-4 receptor (IL-4R), orchestrate type 2 immunity to helminth infections and toxins. Activation of epithelial and myeloid cells, and a transient neutrophils influx initiates type 2 immune responses, which are dominated by basophils, eosinophils, mast cells, B cell immunoglobulin E production, and type 2 T helper and T follicular helper cells. Interestingly, IL-4 and IL-13 can curtail chemotaxis and several effector functions of neutrophils in mice and humans. This inhibitory role of IL-4 and IL-13 probably developed to limit tissue damage by neutrophils during type 2 immunity where a “weep and sweep” response aims at expulsion and decreased fecundity, instead of killing, of macroparasites. Here, we review when IL-4R signaling cytokines appeared during evolution relative to neutrophils and adaptive immunity. Neutrophil-like granular phagocytes were present in invertebrates throughout the bilaterian clade, but we were unable to find data on IL-4, IL-13, or their receptors in invertebrates. Conversely, vertebrates had both adaptive immunity and IL-4, IL-13, and IL-4Rs, suggesting that type 2 cytokines evolved together with adaptive immunity. Further studies are necessary to determine whether IL-4R signaling in neutrophils was established simultaneously with the appearance of adaptive immunity or later.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Immunology
Life Sciences > Genetics
Health Sciences > Genetics (clinical)
Uncontrolled Keywords:Genetics(clinical), Immunology, Genetics
Language:English
Date:1 May 2020
Deposited On:15 Feb 2021 11:43
Last Modified:16 Feb 2021 21:01
Publisher:Nature Publishing Group
ISSN:1466-4879
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41435-020-0095-7
PubMed ID:32139893

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