Mechanisms of asthma and allergic inflammationIL-13 receptor α 2: A regulator of IL-13 and IL-4 signal transduction in primary human fibroblasts
Section snippets
Reagents
Eotaxin ELISA kit, recombinant shIL-4Rα and shIL-13Rα2.Fc, and anti-IL-13Rα2 antibody were obtained from R&D Systems (Abingdon, United Kingdom). Recombinant IL-13 and IL-4 were purchased from Peprotech (London, United Kingdom). A monoclonal anti-IL-13Rα2 from Diaclone (IDS, Boldon, Tyne and Wear, United Kingdom) was used for neutralization experiments and FACs assays, and an anti-IL-13Rα2 from R&D Systems was used for immunoprecipitation experiments.
Primary human cell culture
Bronchial fibroblasts were grown from
Neutralization of IL-13 by soluble IL-13Rα2
We first investigated the ability of a recombinant soluble form of IL-13Rα2 that lacked the transmembrane and cytoplasmic domain of the receptor (shIL-13Rα2) to attenuate responses to IL-13 or IL-4 in fibroblasts. Increasing amounts of shIL-13Rα2 were preincubated with IL-13 or IL-4 for 6 hours before being added to fibroblasts for 24 hours. The supernatants were then collected and assayed for eotaxin release by means of ELISA. Although soluble human IL-4 receptor α (shIL13Rα2) inhibited
Discussion
Many cytokines, such as IL-5, IL-6, and IL-9, have soluble receptors31 that modulate their functions. Production of these isoforms can occur either through alternative splicing or through proteolytic cleavage of the membrane-anchored protein from the cell surface. Although some soluble receptors, such as the soluble IL-6 receptor, are agonists, most soluble receptors are antagonists because they compete with their membrane counterparts for their ligands. In the present study we show that
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2020, Journal of Allergy and Clinical ImmunologyCitation Excerpt :The ligation of receptors initiates the activation of the signal transducer and activator of transcription 6 pathway.97 IL-13 receptor alpha 2 is a decoy receptor and was shown to be a powerful negative regulator of IL-4/IL-13 signaling in human fibroblasts.98 Although they share the same signaling pathway, IL-4 and IL-13 have distinct roles in the pathogenesis of allergic immune responses.
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2019, Autoimmunity ReviewsCitation Excerpt :As this regards, when a cell co-expresses both receptors, IL-13-mediated STAT6 phosphorylation is generally inhibited because of the preferential binding of IL-13 to type 2 IL-13R [10]. On the other hand, IL-13Rα2 can inhibit IL-4-induced STAT6 phosphorylation and interact with IL-4Rα in the absence of IL-13, although IL-13Rα2 does not bind IL-4 [11,12]. Accordingly, it seems that the IL-13Rα2 is able to mediate inhibition of type 1 IL-13Rα1/IL-4Rα receptor signaling by further mechanisms in addition to scavenging IL-13.
Dr Andrews is funded by Asthma UK.
Disclosure of potential conflict of interest: S. T. Holgate has consultant arrangements with and is on the speakers' bureau for Novartis. D. E. Davies has consultant arrangements with and owns stock in Synairgen. The rest of the authors declare that they have no conflict of interest.