(Translated by https://www.hiragana.jp/)
Interleukin Profiling in Atopic Dermatitis and Chronic Nodular Prurigo

Interleukin Profiling in Atopic Dermatitis and Chronic Nodular Prurigo

Int J Mol Sci. 2024 Aug 2;25(15):8445. doi: 10.3390/ijms25158445.

Abstract

The clinical manifestations of atopic dermatitis (AD) and chronic nodular prurigo (CNPG) include pruritus and eczema/lesions, posing significant challenges for patients. Th2 cells and ILC2, marked by cytokine production-particularly IL-4/13-are crucial therapeutic targets. Despite displaying a dose-dependent lack of pruritus induction post-injection, IL-13 acts through the IL-13Rαあるふぁ1 and IL-13Rαあるふぁ2 receptor system. Our study focused on investigating ex vivo skin biopsies in AD (n = 17), CNPG (n = 14) and healthy controls (HC; n = 10), examining the gene expression landscape of interleukins linked with pruritus (IL-13, IL-4, IL-31) and their corresponding receptors. Compared to HC, results revealed a significant upregulation of IL-4, IL-13, and IL-13RA1 in AD, whereas CNPG did not show increased IL13 expression. Notably, the decoy receptor IL-13RA2 displayed intriguing patterns, with AD showing a marked increase compared to both HC and CNPG. Positive correlations between receptor expression and itch intensity and hyperkinesis sensation underscore clinical relevance, potentially serving as biomarkers. The findings suggest a pivotal role of IL-4 and IL-13, along with IL-13RA1, in pruritus pathogenesis in both entities, while IL-13 upregulation in AD is countered by IL-13RA2. The comparable expression of IL-13RA2 to HC in CNPG suggests the absence of this regulatory mechanism, potentially worsening the disease and leading to prolonged scratching behavior. These insights illuminate the intricate interplay of interleukins and receptors in different pruritus phenotypes, laying the groundwork for understanding underlying mechanisms and offering avenues for therapeutic intervention.

Keywords: atopic dermatitis; chronic pruritus; interleukin-13; interleukin-4; nodular prurigo.

MeSH terms

  • Adult
  • Chronic Disease
  • Dermatitis, Atopic* / genetics
  • Dermatitis, Atopic* / immunology
  • Dermatitis, Atopic* / metabolism
  • Dermatitis, Atopic* / pathology
  • Female
  • Humans
  • Interleukin-13 Receptor alpha1 Subunit / genetics
  • Interleukin-13 Receptor alpha1 Subunit / metabolism
  • Interleukin-13 Receptor alpha2 Subunit / genetics
  • Interleukin-13 Receptor alpha2 Subunit / metabolism
  • Interleukin-13* / genetics
  • Interleukin-13* / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Interleukins* / genetics
  • Interleukins* / metabolism
  • Male
  • Middle Aged
  • Prurigo* / genetics
  • Prurigo* / metabolism
  • Prurigo* / pathology
  • Pruritus* / genetics
  • Pruritus* / metabolism
  • Skin / metabolism
  • Skin / pathology
  • Young Adult

Substances

  • Interleukin-13
  • Interleukins
  • Interleukin-4
  • IL31 protein, human
  • IL13 protein, human
  • Interleukin-13 Receptor alpha1 Subunit
  • IL13RA1 protein, human
  • Interleukin-13 Receptor alpha2 Subunit
  • IL4 protein, human