title: Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor α2.
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 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.
authors: Section of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520-8057, USA.
authors: Chuan Hua
authors: CH
authors: He
authors: Chun Geun
authors: CG
authors: Lee
authors: Charles S
authors: CS
authors: Dela Cruz
authors: Chang-Min
authors: CM
authors: Lee
authors: Yang
authors: Y
authors: Zhou
authors: Farida
authors: F
authors: Ahangari
authors: Bing
authors: B
authors: Ma
authors: Erica L
authors: EL
authors: Herzog
authors: Stephen A
authors: SA
authors: Rosenberg
authors: Yue
authors: Y
authors: Li
authors: Adel M
authors: AM
authors: Nour
authors: Chirag R
authors: CR
authors: Parikh
authors: Insa
authors: I
authors: Schmidt
authors: Yorgo
authors: Y
authors: Modis
authors: Lloyd
authors: L
authors: Cantley
authors: Jack A
authors: JA
authors: Elias
mesh_terms: D000818:Animals; D017209:Apoptosis; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D011485:Protein Binding; D016212:Transforming Growth Factor beta / Q000378:metabolism; D060449:Wnt Signaling Pathway
chemical_list: C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D058847:Inflammasomes; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D016212:Transforming Growth Factor beta
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