title: Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice.
abstract: The cytokine thymic stromal lymphopoietin (TSLP) has been linked to human allergic inflammatory diseases. We show here that TSLP expression was increased in the lungs of mice with antigen-induced asthma, whereas TSLP receptor-deficient mice had considerably attenuated disease. Lung-specific expression of a Tslp transgene induced airway inflammation and hyperreactivity characterized by T helper type 2 cytokines and increased immunoglobulin E. The lungs of Tslp-transgenic mice showed massive infiltration of leukocytes, goblet cell hyperplasia and subepithelial fibrosis. TSLP was capable of activating bone marrow-derived dendritic cells to upregulate costimulatory molecules and produce the T helper type 2 cell-attracting chemokine CCL17. These findings suggest that TSLP is an important factor necessary and sufficient for the initiation of allergic airway inflammation.
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, Washington 98101, USA.
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhou
authors.forename: Michael R
authors.initials: MR
authors.lastname: Comeau
authors.forename: Thibaut
authors.initials: T
authors.lastname: De Smedt
authors.forename: H Denny
authors.initials: HD
authors.lastname: Liggitt
authors.forename: Martin E
authors.initials: ME
authors.lastname: Dahl
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
authors.forename: Dora
authors.initials: D
authors.lastname: Gyarmati
authors.forename: Theingi
authors.initials: T
authors.lastname: Aye
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Campbell
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology; D007136:Immunoglobulins; D007249:Inflammation / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000009:adverse effects; D011658:Pulmonary Fibrosis / Q000473:pathology; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics; D015854:Up-Regulation; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D019742:Chemokines, CC; D016207:Cytokines; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse