TNF is required for TLR ligand–mediated but not protease-mediated allergic airway inflammation
| Autor: | Keiko Nakano, Seddon Y. Thomas, Karim H. Shalaby, James M. Ward, Gordon P. Flake, Hideki Nakano, Donald N. Cook, Gregory S. Whitehead, Timothy P. Moran |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Neutrophils Ligands Allergic sensitization Mice 0302 clinical medicine Eosinophilic Lung Mice Knockout biology Interleukin-17 Toll-Like Receptors Cell Differentiation General Medicine respiratory system Cytokines Tumor necrosis factor alpha Interleukin 17 Bronchial Hyperreactivity medicine.symptom Signal Transduction Research Article Proteases Ovalbumin Inflammation 03 medical and health sciences Th2 Cells Hypersensitivity Respiratory Hypersensitivity medicine Animals Asthma Tumor Necrosis Factor-alpha business.industry Allergens medicine.disease respiratory tract diseases Eosinophils Mice Inbred C57BL Disease Models Animal 030104 developmental biology 030228 respiratory system Immunology biology.protein Th17 Cells business |
| DOI: | 10.17615/hx4p-q815 |
| Popis: | Asthma is associated with exposure to a wide variety of allergens and adjuvants. The extent to which overlap exists between the cellular and molecular mechanisms triggered by these various agents is poorly understood, but it might explain the differential responsiveness of patients to specific therapies. In particular, it is unclear why some, but not all, patients benefit from blockade of TNF. Here, we characterized signaling pathways triggered by distinct types of adjuvants during allergic sensitization. Mice sensitized to an innocuous protein using TLR ligands or house dust extracts as adjuvants developed mixed eosinophilic and neutrophilic airway inflammation and airway hyperresponsiveness (AHR) following allergen challenge, whereas mice sensitized using proteases as adjuvants developed predominantly eosinophilic inflammation and AHR. TLR ligands, but not proteases, induced TNF during allergic sensitization. TNF signaled through airway epithelial cells to reprogram them and promote Th2, but not Th17, development in lymph nodes. TNF was also required during the allergen challenge phase for neutrophilic and eosinophilic inflammation. In contrast, TNF was dispensable for allergic airway disease in a protease-mediated model of asthma. These findings might help to explain why TNF blockade improves lung function in only some patients with asthma. |
| Databáze: | OpenAIRE |
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