Nunomura, SatoshiUta, DaisukeKitajima, IsaoNanri, YasuhiroMatsuda, KosukeEjiri, NaokoKitajima, MidoriIkemitsu, HitoshiKoga, MisakiYamamoto, SayakaHonda, YukoTakedomi, HironobuAndoh, TsugunobuConway, Simon J.Izuhara, Kenji2024-11-182024-11-182023Nunomura S, Uta D, Kitajima I, et al. Periostin activates distinct modules of inflammation and itching downstream of the type 2 inflammation pathway. Cell Rep. 2023;42(1):111933. doi:10.1016/j.celrep.2022.111933https://hdl.handle.net/1805/44599Atopic 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.en-USPublisher PolicyImmunologyAtopic dermatitisIntegrinItchingNeutrophilPeriostinArticle