Skin-Derived TSLP Triggers Progression from Epidermal-Barrier Defects to Asthma
被引:172
作者:
Demehri, Shadmehr
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Demehri, Shadmehr
[1
,2
]
Morimoto, Mitsuru
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Morimoto, Mitsuru
[1
,2
]
Holtzman, Michael J.
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h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Holtzman, Michael J.
[3
]
Kopan, Raphael
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Kopan, Raphael
[1
,2
]
机构:
[1] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
[2] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
Asthma is a common allergic lung disease frequently affecting individuals with a prior history of eczema/atopic dermatitis (AD); however, the mechanism underlying the progression from AD to asthma (the so-called "atopic march'') is unclear. Here we show that, like humans with AD, mice with skin-barrier defects develop AD-like skin inflammation and are susceptible to allergic asthma. Furthermore, we show that thymic stromal lymphopoietin (TSLP), overexpressed by skin keratinocytes, is the systemic driver of this bronchial hyper-responsiveness. As an AD-like model, we used mice with keratinocyte-specific deletion of RBP-j that sustained high systemic levels of TSLP. Antigen-induced allergic challenge to the lung airways of RBP-j-deficient animals resulted in a severe asthmatic phenotype not seen in similarly treated wild-type littermates. Elimination of TSLP signaling in these animals blocked the atopic march, demonstrating that high serum TSLP levels were required to sensitize the lung to allergic inflammation. Furthermore, we analyzed outbred K14-TSLPtg mice that maintained high systemic levels of TSLP without developing any skin pathology. Importantly, epidermal-derived TSLP was sufficient to trigger the atopic march, sensitizing the lung airways to inhaled allergens in the absence of epicutaneous sensitization. Based on these findings, we propose that in addition to early treatment of the primary skin-barrier defects, selective inhibition of systemic TSLP may be the key to blocking the development of asthma in AD patients.
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Aberg, Karin M.
;
Man, Mao-Qiang
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Man, Mao-Qiang
;
Gallo, Richard L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Dermatol, San Diego, CA 92103 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Gallo, Richard L.
;
Ganz, Tomas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, Sch Med, Div Pulm, Los Angeles, CA USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Ganz, Tomas
;
Crumrine, Debra
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Crumrine, Debra
;
Brown, Barbara E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Feingold, Kenneth R.
;
Elias, Peter M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Demehri, Shadmehr
;
Liu, Zhenyi
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Liu, Zhenyi
;
Lee, Jonghyeob
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Lee, Jonghyeob
;
Lin, Meei-Hua
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Lin, Meei-Hua
;
Crosby, Seth D.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Crosby, Seth D.
;
Roberts, Christopher J.
论文数: 0引用数: 0
h-index: 0
机构:
Rosetta Inpharmat, Seattle, WA USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Roberts, Christopher J.
;
Grigsby, Perry W.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Grigsby, Perry W.
;
Miner, Jeffrey H.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Miner, Jeffrey H.
;
Farr, Andrew G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA
Univ Washington, Dept Immunol, Seattle, WA 98195 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Farr, Andrew G.
;
Kopan, Raphael
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
He, Rui
;
Oyoshi, Michiko K.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Oyoshi, Michiko K.
;
Garibyan, Lilit
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h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Garibyan, Lilit
;
Kumar, Lalit
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Kumar, Lalit
;
Ziegler, Steven F.
论文数: 0引用数: 0
h-index: 0
机构:
Benaroya Res Inst Viriginia Mason, Program Immunol, Seattle, WA 98101 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Ziegler, Steven F.
;
Geha, Raif S.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Aberg, Karin M.
;
Man, Mao-Qiang
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Man, Mao-Qiang
;
Gallo, Richard L.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Diego, Dept Dermatol, San Diego, CA 92103 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Gallo, Richard L.
;
Ganz, Tomas
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Los Angeles, Sch Med, Div Pulm, Los Angeles, CA USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Ganz, Tomas
;
Crumrine, Debra
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Crumrine, Debra
;
Brown, Barbara E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
Feingold, Kenneth R.
;
Elias, Peter M.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
Univ Calif San Francisco, Vet Affairs Med Ctr, Dermatol & Med Metabolism Serv, San Francisco, CA 94143 USAUniv Kiel, Dept Dermatol, D-2300 Kiel, Germany
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Demehri, Shadmehr
;
Liu, Zhenyi
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Liu, Zhenyi
;
Lee, Jonghyeob
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Lee, Jonghyeob
;
Lin, Meei-Hua
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Lin, Meei-Hua
;
Crosby, Seth D.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Crosby, Seth D.
;
Roberts, Christopher J.
论文数: 0引用数: 0
h-index: 0
机构:
Rosetta Inpharmat, Seattle, WA USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Roberts, Christopher J.
;
Grigsby, Perry W.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Grigsby, Perry W.
;
Miner, Jeffrey H.
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Miner, Jeffrey H.
;
Farr, Andrew G.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA
Univ Washington, Dept Immunol, Seattle, WA 98195 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Farr, Andrew G.
;
Kopan, Raphael
论文数: 0引用数: 0
h-index: 0
机构:
Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USAWashington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
He, Rui
;
Oyoshi, Michiko K.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Oyoshi, Michiko K.
;
Garibyan, Lilit
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Garibyan, Lilit
;
Kumar, Lalit
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Kumar, Lalit
;
Ziegler, Steven F.
论文数: 0引用数: 0
h-index: 0
机构:
Benaroya Res Inst Viriginia Mason, Program Immunol, Seattle, WA 98101 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Ziegler, Steven F.
;
Geha, Raif S.
论文数: 0引用数: 0
h-index: 0
机构:
Harvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA
Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USAHarvard Univ, Sch Med, Div Immunol, Childrens Hosp, Boston, MA 02115 USA