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

Genes and Immunity
Lukas E M HeebOnur Boyman

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 necessa...Continue Reading

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Citations

Jul 16, 2020·International Journal of Molecular Sciences·Shirin KahremanyGuy Cohen
Aug 5, 2020·Immunological Investigations·Shokrollah AssarGholamhossein Hassanshahi
Jul 10, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Federica BottiglioneAdam F L Hurlstone
Jun 3, 2020·Allergy·Ioana AgacheMarek Jutel
Dec 10, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mark J McVeyNeil M Goldenberg
Mar 16, 2021·Frontiers in Immunology·Edgar Ramos-MartínezMarco V José
Apr 4, 2021·International Journal of Molecular Sciences·Jingwei ShiMarko Kornmann
Jun 14, 2020·Journal of the American Academy of Dermatology·Donovan G KearnsJashin J Wu

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