Periostin activates distinct modules of inflammation and itching downstream of the type 2 inflammation pathway
Satoshi Nunomura 1, Daisuke Uta 2, Isao Kitajima 3, Yasuhiro Nanri 4, Kosuke Matsuda 2, Naoko Ejiri 3, Midori Kitajima 3, Hitoshi Ikemitsu 4, Misaki Koga 4, Sayaka Yamamoto 4, Yuko Honda 4, Hironobu Takedomi 4, Tsugunobu Andoh 5, Simon J Conway 6, Kenji Izuhara 7
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.
