Genetic Variation Determines Mast Cell Functions in Experimental Asthma
| Autor: | Christian Taube, Matthias Klein, Markus P. Radsak, Marc Becker, Michael Stassen, Hansjörg Schild, Anastasija Michel, Tobias Bopp, Pamela Friedrich, Edgar Schmitt, Sebastian Reuter, Fatma Doener, Bernd Echtenacher |
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| Rok vydání: | 2011 |
| Předmět: |
Immunology
Congenic Cell Count Inflammation Immunoglobulin E Mice Mice Congenic Th2 Cells Immune system medicine Animals Immunology and Allergy Mast Cells Sensitization Asthma Polymorphism Genetic biology medicine.disease Mast cell Interleukin 33 medicine.anatomical_structure biology.protein Bronchial Hyperreactivity medicine.symptom |
| Zdroj: | The Journal of Immunology. 186:7225-7231 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1100676 |
| Popis: | Mast cell-deficient mice are a key for investigating the function of mast cells in health and disease. Allergic airway disease induced as a Th2-type immune response in mice is employed as a model to unravel the mechanisms underlying inception and progression of human allergic asthma. Previous work done in mast cell-deficient mouse strains that otherwise typically mount Th1-dominated immune responses revealed contradictory results as to whether mast cells contribute to the development of airway hyperresponsiveness and airway inflammation. However, a major contribution of mast cells was shown using adjuvant-free protocols to achieve sensitization. The identification of a traceable genetic polymorphism closely linked to the KitW-sh allele allowed us to generate congenic mast cell-deficient mice on a Th2-prone BALB/c background, termed C.B6-KitW-sh. In accordance with the expectations, C.B6-KitW-sh mice do not develop IgE- and mast cell-dependent passive cutaneous anaphylaxis. Yet, unexpectedly, C.B6-KitW-sh mice develop full-blown airway inflammation, airway hyperresponsiveness, and mucus production despite the absence of mast cells. Thus, our findings demonstrate a major influence of genetic background on the contribution of mast cells in an important disease model and introduce a novel strain of mast cell-deficient mice. |
| Databáze: | OpenAIRE |
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