Epithelial Cell-Derived IL-25, but Not Th17 Cell-Derived IL-17 or IL-17F, Is Crucial for Murine Asthma

作者：Suzukawa Maho; Morita Hideaki; Nambu Aya; Arae Ken; Shimura Eri; Shibui Akiko; Yamaguchi Sachiko; Suzukawa Keigo; Nakanishi Wakako; Oboki Keisuke; Kajiwara Naoki; Ohno Tatsukuni; Ishii Akina; Koerner Heinrich; Cua Daniel J; Suto Hajime; Yoshimoto Takayuki; Iwakura Yoichiro; Yamasoba Tatsuya; Ohta Ken; Sudo Katsuko; Saito Hirohisa; Okumura Ko; Broide David H; Matsumoto Kenji; Nakae Susumu^*

来源：The Journal of Immunology, 2012, 189(7): 3641-3652.

DOI：10.4049/jimmunol.1200461

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)-gamma t-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. The Journal of Immunology, 2012, 189: 3641-3652.

• 出版日期2012-10-1
• 单位河北医科大学