Cell Reports
Volume 4, Issue 4, 29 August 2013, Pages 830-841
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Article
Chitinase 3-like 1 Regulates Cellular and Tissue Responses via IL-13 Receptor α2

https://doi.org/10.1016/j.celrep.2013.07.032Get rights and content
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Highlights

  • Chi3l1 binds to IL-13Rα2 and stimulates MAPK, Akt/PKB, and Wnt//β-catenin signaling

  • Chi3l1 regulates oxidant injury, apoptosis, and pyroptosis via IL-13Rα2

  • Chi3l1 regulates antibacterial response and inflammasome activation via IL-13Rα2

  • Chi3l1 regulates melanoma metastasis and TGF-β1 production via IL-13Rα2

Summary

Members of the 18 glycosyl hydrolase (GH 18) gene family have been conserved over species and time and are dysregulated in inflammatory, infectious, remodeling, and neoplastic disorders. This is particularly striking for the prototypic chitinase-like protein chitinase 3-like 1 (Chi3l1), which plays a critical role in antipathogen responses where it augments bacterial killing while stimulating disease tolerance by controlling cell death, inflammation, and remodeling. However, receptors that mediate the effects of GH 18 moieties have not been defined. Here, we demonstrate that Chi3l1 binds to interleukin-13 receptor α2 (IL-13Rα2) and that Chi3l1, IL-13Rα2, and IL-13 are in a multimeric complex. We also demonstrate that Chi3l1 activates macrophage mitogen-activated protein kinase, protein kinase B/AKT, and Wnt/β-catenin signaling and regulates oxidant injury, apoptosis, pyroptosis, inflammasome activation, antibacterial responses, melanoma metastasis, and TGF-β1 production via IL-13Rα2-dependent mechanisms. Thus, IL-13Rα2 is a GH 18 receptor that plays a critical role in Chi3l1 effector responses.

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This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Present address: Brown University, Warren Alpert Medical School, Box G-A1, 97 Waterman Street, Providence, RI 02912, USA