Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK.
Allergic asthma patients manifest airway inflammation and some show increases in eosinophils, T(H)2 cells, and cytokines, increased mucous production in the lung, and elevated serum IgE. This T(H)2-type response suggests a prominent role for T(H)2 cells and their cytokines in the pathology of this disease. The Tec family nonreceptor tyrosine kinase inducible T cell kinase (ITK) has been shown to play a role in the differentiation and/or function of T(H)2-type cells, suggesting that ITK may represent a good target for the control of asthma. Using a murine model of allergic asthma, we show here that ITK is involved in the development of immunological symptoms seen in this model. We show that mice lacking ITK have drastically reduced lung inflammation, eosinophil infiltration, and mucous production following induction of allergic asthma. Notably, T cell influx into the lung was reduced in mice lacking ITK. T cells from ITK(-/-) mice also exhibited reduced proliferation and cytokine secretion, in particular IL-5 and IL-13, in response to challenge with the allergen OVA, despite elevated levels of total IgE and increased OVA-specific IgE responses. Our results suggest that the tyrosine kinase ITK preferentially regulates the secretion of the T(H)2 cytokines IL-5 and IL-13 and may be an attractive target for antiasthmatic drugs.
Immunology Research Laboratories and Department of Veterinary Science, Pennsylvania State University, University Park, PA 16802, USA.
Cynthia
C
Mueller
Avery
A
August
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D000485:Allergens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007073:Immunoglobulin E; D010047:Ovalbumin; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase