The Interleukin-13 Receptor-α1 Chain Is Essential for Induction of the Alternative Macrophage Activation Pathway by IL-13 but Not IL-4

Journal of Innate Immunity
Faruk SheikhRaymond P Donnelly

Abstract

Macrophages coexpress both the interleukin (IL)-2Rγ chain (γ(c)) and IL-13Rα1. These receptor chains can heterodimerize with IL-4Rα to form type I or type II IL-4 receptor complexes, respectively. We used macrophages derived from Il2rg and Il13ra1 knockout (KO) mice to evaluate the requirements for these receptor chains for induction of the alternative macrophage activation (AMA) pathway by IL-4 and IL-13. Absence of γ(c) significantly decreased activation of STAT6 by IL-4 but not IL-13. However, although activation of STAT6 by IL-4 was markedly reduced in γ(c) KO macrophages, it was not abolished, indicating that IL-4 can still signal through type II IL-4 receptors via the IL-13Rα1 chain. IL-13 failed to activate STAT6 in macrophages derived from Il13ra1 KO mice; however, these cells remained fully responsive to IL-4. The inability of IL-13 but not IL-4 to signal in Il13ra1(-/-) macrophages correlated with the inability of IL-13 but not IL-4 to induce expression of genes such as Arg1, Retnla and Ccl11 that are characteristically expressed by alternatively activated macrophages. In addition, IL-13 but not IL-4 failed to induce membrane fusion and giant cell formation by Il13ra1 KO macrophages. These findings demonstrate that th...Continue Reading

Citations

Jun 14, 2015·Cytokine·Naina Gour, Marsha Wills-Karp
Nov 5, 2016·International Journal of Pharmaceutics·Adam C FisherJanet Woodcock
Feb 12, 2017·Pflügers Archiv : European journal of physiology·Siamon Gordon, Luisa Martinez-Pomares
Oct 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Dylan J WodsedalekCaitlin C O'Meara
Sep 9, 2017·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Seung Hee HaJin Han
Mar 13, 2020·JCI Insight·Rajesh Kumar RadhakrishnanRamakrishna Vankayalapati

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