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

Area of Science:

• Immunology
• Molecular Biology
• Biochemistry

Background:

• Glycosyl hydrolase (GH 18) family proteins are crucial in various biological processes and diseases.
• Chitinase 3-like 1 (Chi3l1) is a key prototypic protein in GH 18, involved in antipathogen responses and disease tolerance.
• The specific receptors mediating the effects of GH 18 proteins, including Chi3l1, remained undefined.

Purpose of the Study:

• To identify the receptor for chitinase 3-like 1 (Chi3l1).
• To elucidate the downstream signaling pathways and biological functions regulated by the Chi3l1-receptor interaction.
• To understand the role of this interaction in various cellular processes and disease contexts.

Main Methods:

• Binding assays to demonstrate the interaction between Chi3l1 and interleukin-13 receptor α2 (IL-13Rα2).
• Co-immunoprecipitation to confirm the formation of a multimeric complex involving Chi3l1, IL-13Rα2, and IL-13.
• Western blotting and reporter assays to assess the activation of signaling pathways (MAPK, AKT, Wnt/β-catenin) and downstream effectors.
• Functional assays to evaluate Chi3l1's role in oxidant injury, apoptosis, pyroptosis, inflammasome activation, antibacterial responses, melanoma metastasis, and TGF-β1 production via IL-13Rα2.

Main Results:

• Chi3l1 was identified to bind specifically to interleukin-13 receptor α2 (IL-13Rα2).
• Chi3l1, IL-13Rα2, and IL-13 form a multimeric complex.
• Chi3l1 activates macrophage signaling pathways, including MAPK, AKT, and Wnt/β-catenin, in an IL-13Rα2-dependent manner.
• Chi3l1 regulates critical cellular processes such as apoptosis, pyroptosis, inflammasome activation, and antibacterial responses through IL-13Rα2.

Conclusions:

• Interleukin-13 receptor α2 (IL-13Rα2) functions as a receptor for chitinase 3-like 1 (Chi3l1).
• The Chi3l1-IL-13Rα2 interaction is critical for mediating Chi3l1's diverse cellular and biological effects.
• This discovery provides a molecular basis for understanding Chi3l1's role in inflammatory, infectious, and neoplastic disorders.