Regulation and dysregulation of CARD14 signalling and its physiological consequences in inflammatory skin disease

Cell Immunol. 2020 Aug:354:104147. doi: 10.1016/j.cellimm.2020.104147. Epub 2020 Jun 13.

Abstract

CARD14 is a scaffold molecule predominantly expressed in keratinocytes and genetic variants in the CARD14 gene confer an increased risk of inflammatory skin disease. Due to its association with common skin diseases psoriasis and atopic dermatitis, the biological function of CARD14 is of relevant interest to human health. CARD14 recruits BCL10 and MALT1 to form the CARD-BCL10-MALT1 complex, which modulates NF-κB and MAPK signalling pathways, yet little is known about how CARD14 is regulated or activated in the context of the innate immune response and in chronic inflammation. This review summarises the current understanding of the molecular function and regulatory mechanisms of CARD14 and highlights recent findings in human disease and murine mouse models.

Keywords: Atopic dermatitis; BCL10; CARD14/CARMA2; Inflammation; Keratinocytes; MALT1; NF-κB; Pityriasis rubra pilaris; Psoriasis.

Publication types

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

MeSH terms

  • Animals
  • B-Cell CLL-Lymphoma 10 Protein / metabolism
  • CARD Signaling Adaptor Proteins
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation
  • Guanylate Kinases
  • Humans
  • Immunity, Innate
  • Inflammation / immunology*
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein / metabolism
  • NF-kappa B / metabolism
  • Signal Transduction
  • Skin / immunology*

Substances

  • B-Cell CLL-Lymphoma 10 Protein
  • CARD Signaling Adaptor Proteins
  • NF-kappa B
  • Extracellular Signal-Regulated MAP Kinases
  • Card14 protein, mouse
  • Guanylate Kinases
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein