Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma.
Atopic dermatitis (AD) is often the initial step in the "atopic march," given that more than half of AD patients with moderate to severe AD develop asthma later in life. Both AD and asthma share a similar "atopy" phenotype that includes T helper type 2 inflammation with eosinophilia and hyper-IgE immunoglobulinemia, but the molecular mechanisms underlying the "atopic march" remain elusive. In the present study, we show that induced expression of thymic stromal lymphopoietin (TSLP) in mouse epidermal keratinocytes upon topical application of MC903 (a low calcemic analogue of vitamin D3) not only triggers AD as we previously reported but also aggravates experimental allergic asthma induced by ovalbumin sensitization and challenge. Our study, which provides a mouse model to study human "atopic march," indicates that keratinocyte-produced TSLP may represent an important factor in the link of atopic dermatitis to asthma.
Zhang
Zhikun
Z
Department of Functional Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, 67404 Illkirch, France.
Hener
Pierre
P
Frossard
Nelly
N
Kato
Shigeaki
S
Metzger
Daniel
D
Li
Mei
M
Chambon
Pierre
P
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D004195:Disease Models, Animal; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse