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New mechanism underlying IL-31-induced atopic dermatitis.

Jianghui Meng1, Masaki Moriyama2, Micha Feld3

  • 1International Center for Neurotherapeutics, Dublin City University, Dublin, Ireland; Department of Dermatology and UCD Charles Institute for Translational Dermatology, Dublin, Ireland.

The Journal of Allergy and Clinical Immunology
|February 11, 2018
PubMed
Summary

Interleukin-31 (IL-31) regulates brain-derived natriuretic peptide (BNP) in atopic dermatitis (AD). This study reveals BNP

Keywords:
Atopic dermatitisbrain-derived natriuretic peptidedendritic cellsdorsal root ganglionkeratinocytespruritogenspruritusskinsoluble N-ethylmaleimide–sensitive factor activating protein receptors

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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.