IL-37 regulates allergic inflammation by counterbalancing pro-inflammatory IL-1 and IL-33

Area of Science:

• Immunology
• Respiratory Medicine
• Molecular Biology

Background:

• Children with asthma exhibit reduced interleukin-37 (IL-37) production.
• IL-37 demonstrates inhibitory effects on experimental allergic asthma (EAA) in mice.
• The precise mechanisms by which IL-37 controls allergic inflammation remain to be elucidated.

Purpose of the Study:

• To identify the cellular targets of IL-37 in the context of allergic inflammation.
• To elucidate the molecular mechanisms underlying IL-37's anti-inflammatory properties in asthma.
• To investigate the role of IL-37 in relation to IL-1β and IL-33 in asthma pathogenesis.

Main Methods:

• Single-cell RNA sequencing was employed to identify IL-37 target cells.
• Gene expression analysis of airway tissues and isolated cells (mononuclear cells and airway epithelial cells) was performed.
• Studies in wild-type and knockout mice, along with analysis of patient samples, were conducted to assess IL-37's function and levels.

Main Results:

• IL-37 targets airway epithelial cells, T cells, and dendritic cells.
• IL-37 modulates gene expression induced by IL-1β and IL-33, reducing Th2 cytokine production and pro-inflammatory mediators.
• IL-37's protective effects in EAA were dependent on IL-1R1 and IL-33 signaling.
• Asthma patients showed increased IL-1β and IL-33 to IL-37 expression ratios.

Conclusions:

• IL-37 exerts its anti-allergic asthma effects by counterbalancing the pro-inflammatory actions of IL-1β and IL-33.
• IL-37 plays a critical role in regulating airway inflammation.
• Findings suggest IL-37 as a potential therapeutic target for asthma.