Interleukin-37 monomer is the active form for reducing innate immunity

Area of Science:

• Immunology
• Biochemistry
• Structural Biology

Background:

• Interleukin-37 (IL-37) is a key cytokine that suppresses innate and acquired immunity.
• Understanding IL-37's structure-function relationship is crucial for its therapeutic potential.

Purpose of the Study:

• To elucidate the unique biophysical, biochemical, and biological characteristics of IL-37.
• To investigate the role of IL-37's monomeric and dimeric forms in its anti-inflammatory activity.

Main Methods:

• Integrative approach combining biophysical, biochemical, and biological studies.
• Site-directed mutagenesis to create stable IL-37 monomers.
• Cell-based assays measuring inflammatory markers like VCAM.

Main Results:

• Monomeric IL-37 forms show significantly higher anti-inflammatory activity than native IL-37 dimers.
• Native IL-37 forms dimers with nanomolar affinity, which can inhibit monomeric activity.
• Heparin binding modulates IL-37 self-association, influencing its suppressive function.

Conclusions:

• IL-37's anti-inflammatory efficacy is concentration-dependent and influenced by its monomer-dimer equilibrium.
• Extended N and C termini of IL-37 are essential for its suppressive activity.
• A model for IL-37 interactions is proposed, explaining its mechanism in suppressing innate inflammation.