Potential involvement of IL-17F in asthma.
The expression of IL-17F is seen in the airway of asthmatics and its level is correlated with disease severity. Several studies have demonstrated that IL-17F plays a pivotal role in allergic airway inflammation and induces several asthma-related molecules such as CCL20. IL-17F-induced CCL20 may attract Th17 cells into the airway resulting in the recruitment of additional Th17 cells to enhance allergic airway inflammation. We have recently identified, for the first time, that bronchial epithelial cells are its novel cell source in response to IL-33 via ST2-ERK1/2-MSK1 signaling pathway. The receptor for IL-17F is the heterodimeric complex of IL-17RA and IL-17RC, and IL-17F activates many signaling pathways. In a case-control study of 867 unrelated Japanese subjects, a His161 to Arg161 (H161R) substitution in the third exon of the IL-17F gene was associated with asthma. In atopic patients with asthma, prebronchodilator baseline FEV1/FVC values showed a significant association with the H161R variant. Moreover, this variant is a natural antagonist for the wild-type IL-17F. Moreover, IL-17F is involved in airway remodeling and steroid resistance. Hence, IL-17F may play an orchestrating role in the pathogenesis of asthma and may provide a valuable therapeutic target for development of novel strategies.
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Kyoko
K
Ota
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Mio
0000-0002-6203-6733
M
Kawaguchi
Department of Respiratory Medicine, Showa University Fujigaoka Hospital, 1-30 Aoba-ku, Yokohama 227-8501, Japan.
Satoshi
S
Matsukura
Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Masatsugu
M
Kurokawa
Department of Respiratory Medicine, Showa University Fujigaoka Hospital, 1-30 Aoba-ku, Yokohama 227-8501, Japan.
Fumio
F
Kokubu
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Junichi
J
Fujita
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Yuko
0000-0002-7407-4243
Y
Morishima
Johns Hopkins University, Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224-6801, USA ; National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan.
Shau-Ku
SK
Huang
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Yukio
Y
Ishii
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Hiroaki
H
Satoh
Division of Clinical Medicine, Department of Respiratory Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8575, Japan.
Nobuyuki
N
Hizawa
D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D004351:Drug Resistance; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D020381:Interleukin-17 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
D020381:Interleukin-17; D053722:Receptors, Interleukin-17