Periostin contributes to the pathogenesis of atopic dermatitis by inducing TSLP production from keratinocytes.
BACKGROUND
Atopic dermatitis (AD) is a chronic inflammatory skin disease where Th2-type immune responses are dominant. Keratinocytes persistently secrete proinflammatory cytokines and chemokines, amplifying Th2-type responses in AD. We have recently reported that periostin, an extracellular matrix protein induced by Th2 cytokines, plays a critical role in AD. In the present study, we have further investigated the characteristics of our allergen-induced AD model mice and the role of periostin in the pathogenesis of AD.


METHODS
The ears of C57BL/6 mice, BALB/c mice, and Rag-2-/- γ(c)-/- mice (BALB/c background) were epicutaneously sensitized repeatedly with HDM. Mice were analyzed after the final sensitization. To examine the direct role of periostin, we reconstituted skin in vitro by coculture of keratinocytes with wild-type or periostin-deficient fibroblasts.


RESULTS
Epicutaneous sensitization with HDM induced AD-like phenotypes and accumulation of periostin in dermis in C57BL/6 mice but not in Rag-2-/- γ(c)-/- mice. In vitro organotypic coculture systems revealed that periostin promoted survival and proliferation of keratinocytes and directly induced production of thymic stromal lymphopoietin (TSLP).


CONCLUSIONS
Our results suggest that periostin exacerbates the pathogenesis of AD through TSLP production from keratinocytes.
Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Japan.
Hiroshi
H
Shiraishi
Miho
M
Masuoka
Shoichiro
S
Ohta
Shoichi
S
Suzuki
Kazuhiko
K
Arima
Kazuto
K
Taniguchi
Shigehisa
S
Aoki
Shuji
S
Toda
Tomohiro
T
Yoshimoto
Naoki
N
Inagaki
Simon J
SJ
Conway
Yutaka
Y
Narisawa
Kenji
K
Izuhara
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
D039741:Antigens, Dermatophagoides; D015815:Cell Adhesion Molecules; D016207:Cytokines; C082838:Postn protein, mouse; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse