Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2

Chuan Hua He, Chun Geun Lee, Charles S. DelaCruz, Chang Min Lee, Yang Zhou, Farida Ahangari, Bing Ma, Erica L. Herzog, Stephen A. Rosenberg, Yue Li, Adel M. Nour, Chirag R. Parikh, Insa Schmidt, Yorgo Modis, Lloyd Cantley, Jack A. Elias

Research output: Contribution to journalArticle

Abstract

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 inantipathogen 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

Original languageEnglish (US)
Pages (from-to)830-841
Number of pages12
JournalCell Reports
Volume4
Issue number4
DOIs
StatePublished - Aug 29 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    He, C. H., Lee, C. G., DelaCruz, C. S., Lee, C. M., Zhou, Y., Ahangari, F., Ma, B., Herzog, E. L., Rosenberg, S. A., Li, Y., Nour, A. M., Parikh, C. R., Schmidt, I., Modis, Y., Cantley, L., & Elias, J. A. (2013). Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2. Cell Reports, 4(4), 830-841. https://doi.org/10.1016/j.celrep.2013.07.032