Interleukin-33 in atopic dermatitis

J Dermatol Sci. 2019 Oct;96(1):2-7. doi: 10.1016/j.jdermsci.2019.08.006. Epub 2019 Aug 19.

Abstract

Atopic dermatitis (AD) is characterized by pruritus, barrier disruption, and inflammationincluding type 2 cytokine production. Interleukin-33 (IL-33) is an inflammatory cytokine that is over-expressed in the keratinocytes of patients with AD. IL-33 transgenic mice, which express IL-33 specifically in keratinocytes, spontaneously develop AD-like eczema, suggesting that IL-33 is sufficient for the development of AD. IL-33 stimulates various cells, including group 2 innate lymphoid cells (ILC2s), to produce type 2 cytokines, such as IL-5 and IL-13, and IL-33-stimulated basophils activate ILC2s via IL-4. ILC2s are enriched in human AD skin lesions, and ILC2 isolated from AD lesions, are activated by IL-33, not by thymic stromal lymphopoietin (TSLP). IL-33 induces IL-31, thereby promoting pruritus and scratching behavior. Conversely, scratching the skin promotes IL-33 release from keratinocytes. IL-33 reduces the expression of filaggrin and claudin-1; it also reduces the skin barrier function. However, barrier destruction causes percutaneous exposure to allergens or IL-33 release. Thus, IL-33 is a common point of entry into the itch-scratch cycle of AD. These new findings can facilitate the development of novel therapeutic drugs targeting IL-33.

Keywords: Atopic dermatitis; Basophils; Group 2 innate lymphoid cells (ILC2s); IL-33; IL-4.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Basophils / immunology
  • Basophils / metabolism
  • Dermatitis, Atopic / drug therapy
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / pathology
  • Disease Models, Animal
  • Filaggrin Proteins
  • Humans
  • Immunity, Innate / drug effects
  • Interleukin-1 Receptor-Like 1 Protein / immunology
  • Interleukin-1 Receptor-Like 1 Protein / metabolism
  • Interleukin-33 / antagonists & inhibitors
  • Interleukin-33 / immunology*
  • Interleukin-33 / metabolism
  • Interleukins / metabolism
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Mice
  • Signal Transduction / immunology
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology

Substances

  • FLG protein, human
  • Filaggrin Proteins
  • IL31 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins