The IL-13-OVOL1-FLG axis in atopic dermatitis

Immunology. 2019 Dec;158(4):281-286. doi: 10.1111/imm.13120. Epub 2019 Oct 1.

Abstract

Despite sharing interleukin-4 receptor α (IL-4Rα) in their signaling cascades, IL-4 and IL-13 have different functions in atopic inflammation. IL-13 preferentially participates in the peripheral tissues because tissue-resident group 2 innate lymphoid cells produce IL-13 but not IL-4. In contrast, lymph node T follicular helper cells express IL-4 but not IL-13 to regulate B-cell immunity. The dominant microenvironment of IL-13 is evident in the lesional skin of atopic dermatitis (AD). The IL-13-rich local milieu causes barrier dysfunction by down-regulating the OVOL1-filaggrin (FLG) axis and up-regulating the periostin-IL-24 axis. Genome-wide association studies also point to the crucial involvement of the IL-13, OVOL1 and FLG genes in the pathogenesis of AD. Biologics targeting IL-13, such as the anti-IL-4Rα antibody dupilumab and the anti-IL-13 antibody tralokinumab, successfully improve AD lesions and further highlight the importance of IL-13 in the pathogenesis of AD.

Keywords: OVOL1; Periostin; atopic dermatitis; filaggrin; interleukin-13.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biological Therapy
  • DNA-Binding Proteins / metabolism*
  • Dermatitis, Atopic / immunology*
  • Dermatitis, Atopic / therapy
  • Filaggrin Proteins
  • Humans
  • Immunity, Innate
  • Interleukin-13 / immunology
  • Interleukin-13 / metabolism*
  • Interleukin-4 Receptor alpha Subunit / immunology
  • Interleukin-4 Receptor alpha Subunit / metabolism*
  • Intermediate Filament Proteins / metabolism*
  • Lymphocytes / immunology*
  • Signal Transduction
  • Skin / immunology*
  • Transcription Factors / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • DNA-Binding Proteins
  • FLG protein, human
  • Filaggrin Proteins
  • IL4R protein, human
  • Interleukin-13
  • Interleukin-4 Receptor alpha Subunit
  • Intermediate Filament Proteins
  • OVOL1 protein, human
  • Transcription Factors
  • dupilumab
  • tralokinumab