Epithelial Cell-Derived IL-25, but Not Th17 Cell-Derived IL-17 or IL-17F, Is Crucial for Murine Asthma
| Autor: | Eri Shimura, Tatsukuni Ohno, Daniel J. Cua, Keigo Suzukawa, Hajime Suto, David H. Broide, Maho Suzukawa, Ko Okumura, Akiko Shibui, Wakako Nakanishi, Yoichiro Iwakura, Tatsuya Yamasoba, Ken Ohta, Sachiko Yamaguchi, Ken Arae, Aya Nambu, Katsuko Sudo, Naoki Kajiwara, Kenji Matsumoto, Keisuke Oboki, Akina Ishii, Hirohisa Saito, Takayuki Yoshimoto, Heinrich Körner, Hideaki Morita, Susumu Nakae |
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| Rok vydání: | 2012 |
| Předmět: |
Adoptive cell transfer
Cellular differentiation Immunology Mice Transgenic Inflammation Immunoglobulin E Article Proinflammatory cytokine Mice Th2 Cells Immune system Eosinophilia Animals Immunology and Allergy Medicine Dendritic cell migration Cells Cultured biology business.industry Interleukins Interleukin-17 Cell Differentiation Epithelial Cells respiratory system Asthma Mice Inbred C57BL Disease Models Animal biology.protein Th17 Cells Female Interleukin 17 Inflammation Mediators medicine.symptom business |
| Zdroj: | The Journal of Immunology. 189:3641-3652 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1200461 |
| Popis: | IL-17A, IL-17F, and IL-25 are ligands for IL-17RA. In the current study, we demonstrated that IL-25–deficient mice—but not IL-17A–, IL-17F–, IL-17A/F–, IL-23p19–, or retinoic acid-related orphan receptor (ROR)-γt–deficient mice—showed significant suppression of 1) the number of eosinophils and the levels of proinflammatory mediators in bronchoalveolar lavage fluids, 2) airway hyperresponsiveness to methacholine, and 3) OVA-specific IgG1 and IgE levels in the serum during OVA-induced Th2-type/eosinophilic airway inflammation. The IL-25 deficiency did not affect lung dendritic cell migration or Ag-specific memory–Th2 cell expansion during Ag sensitization. Adoptive transfer of T cells, mast cells, or bone marrow cells from IL-25–deficient mice revealed that induction of Th2-type/eosinophilic airway inflammation was dependent on activation of lung epithelial cells and eosinophils by IL-25 produced by airway structural cells such as epithelial cells but not by such hematopoietic stem-cell-origin immune cells as T cells and mast cells. Therefore, airway structural cell-derived IL-25—rather than Th17 cell-derived IL-17A and IL-17F—is responsible for induction of local inflammation by promoting activation of lung epithelial cells and eosinophils in the elicitation phase of Th2-type/eosinophilic airway inflammation. It is not required for Ag-specific Th2 cell differentiation in the sensitization phase. |
| Databáze: | OpenAIRE |
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