Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice.
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.
Zhou
Baohua
B
Immunology Program, Benaroya Research Institute, Seattle, Washington 98101, USA.
Comeau
Michael R
MR
De Smedt
Thibaut
T
Liggitt
H Denny
HD
Dahl
Martin E
ME
Lewis
David B
DB
Gyarmati
Dora
D
Aye
Theingi
T
Campbell
Daniel J
DJ
Ziegler
Steven F
SF
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
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