Periostin activates distinct modules of inflammation and itching downstream of the type 2 inflammation pathway

Cell Rep. 2023 Jan 31;42(1):111933. doi: 10.1016/j.celrep.2022.111933. Epub 2023 Jan 6.

Abstract

Atopic dermatitis (AD) is a chronic relapsing skin disease accompanied by recurrent itching. Although type 2 inflammation is dominant in allergic skin inflammation, it is not fully understood how non-type 2 inflammation co-exists with type 2 inflammation or how type 2 inflammation causes itching. We have recently established the FADS mouse, a mouse model of AD. In FADS mice, either genetic disruption or pharmacological inhibition of periostin, a downstream molecule of type 2 inflammation, inhibits NF-κB activation in keratinocytes, leading to downregulating eczema, epidermal hyperplasia, and infiltration of neutrophils, without regulating the enhanced type 2 inflammation. Moreover, inhibition of periostin blocks spontaneous firing of superficial dorsal horn neurons followed by a decrease in scratching behaviors due to itching. Taken together, periostin links NF-κB-mediated inflammation with type 2 inflammation and promotes itching in allergic skin inflammation, suggesting that periostin is a promising therapeutic target for AD.

Keywords: CP: Immunology; atopic dermatitis; integrin; itching; neutrophil; periostin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dermatitis, Atopic* / etiology
  • Inflammation / metabolism
  • Keratinocytes / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Pruritus / metabolism
  • Skin* / metabolism

Substances

  • NF-kappa B