New mechanism underlying IL-31-induced atopic dermatitis

Area of Science:

• Neuroimmunology
• Dermatology
• Pruritus Research

Background:

• Atopic dermatitis (AD) is a chronic skin disorder where IL-31 is a key mediator.
• Brain-derived natriuretic peptide (BNP) is known to mediate itch, but its role in skin-derived itch and its link to IL-31 in AD remain unclear.

Purpose of the Study:

• To investigate the role of BNP in peripheral sensory systems and skin.
• To examine BNP's function in IL-31-induced itch and neuro-immune interactions in AD.

Main Methods:

• Utilized Ca2+ imaging, immunohistochemistry, qPCR, RNA sequencing, and pharmacologic inhibition.
• Studied dorsal root ganglionic neurons (DRGs), skin cells, AD mouse models, and human skin samples from AD patients and healthy subjects.

Main Results:

• IL-31 upregulated BNP in murine DRGs and induced BNP release, correlating with AD-like dermatitis severity.
• Increased BNP and its receptor expression were observed in the skin of AD patients.
• BNP stimulation induced a pro-inflammatory and itch-promoting phenotype in human skin cells.

Conclusions:

• BNP is implicated in AD pathogenesis, with IL-31 regulating its synthesis and release in both DRGs and skin.
• IL-31 coordinates itch signaling pathways by modulating BNP and skin cell cytokine release.
• Targeting peripheral BNP function presents a potential therapeutic strategy for AD and other pruritic conditions.