IL‑37/IL‑1R8 blocks keratinocyte acantholysis via suppressing ADAM17/EGFR.

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Pemphigus vulgaris (PV) is a severe autoimmune blistering disease.
• Keratinocyte acantholysis drives PV progression.
• The role and receptor of Interleukin-37 (IL-37) in PV are not fully understood.

Purpose of the Study:

• To investigate the mechanism of IL-37's protective effect in PV.
• To identify the specific receptor for IL-37 in PV.
• To elucidate the signaling pathway involved in IL-37's action.

Main Methods:

• Quantified IL-37 levels in PV patients.
• Treated keratinocytes with IL-37.
• Utilized co-immunoprecipitation to identify IL-37 binding partners.
• Performed gene knockdown of IL-1 receptor 8 (IL-1R8).
• Assessed effects on acantholysis, apoptosis, and signaling pathways (EGFR, ADAM17).

Main Results:

• Elevated IL-37 levels were observed in PV patients.
• IL-37 treatment inhibited keratinocyte acantholysis and apoptosis.
• IL-37 directly binds to IL-1 receptor 8 (IL-1R8).
• IL-1R8 knockdown abrogated IL-37's protective effects.
• The IL-37/IL-1R8 complex suppressed EGFR signaling and reduced ADAM17 expression.

Conclusions:

• IL-37 treatment attenuates PV by inhibiting keratinocyte dissociation and apoptosis.
• The mechanism involves the IL-1R8/ADAM17/EGFR pathway.
• IL-37 exerts a protective role in PV via IL-1R8.