title: IL-17A/F modulates fibrocyte functions in cooperation with CD40-mediated signaling.
abstract: T helper 17 (Th17) cells that produce interleukin (IL)-17A and IL-17F have been found to participate in the development of bronchial asthma and bleomycin-induced pulmonary fibrosis. However, whether they play a causative role in the airway remodeling observed in these respiratory diseases remains unclear. Because fibrocytes are involved in tissue repair and fibrosis and are presumably precursors of lung fibroblasts and myofibroblasts, we examined the effects of IL-17A/F on fibrocyte functions. Both IL-17A and IL-17F enhanced fibrocytes' α-smooth muscle actin expression. Priming fibrocytes with IL-17A enhanced their CD40-mediated IL-6 production, whereas IL-17F-priming increased the CD40-mediated mRNA expression of collagen I, vascular endothelial growth factor, and angiogenin. CD4(+) T cells co-cultured with fibrocytes produced IL-17A, which was inhibited by blocking CD40 and CD40 ligand interactions. These findings suggest that cooperative interactions between fibrocytes and Th17 cells play an important role via CD40- and IL-17A/F-mediated signaling for collagen and proangiogenic factor production, which may lead to the extracellular matrix deposition and neovascularization seen in airway remodeling.
authors: Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida-gun, Fukui 910-1193, Japan.
authors: Hisako
authors: H
authors: Hayashi
authors: Akiko
authors: A
authors: Kawakita
authors: Shintaro
authors: S
authors: Okazaki
authors: Motoko
authors: M
authors: Yasutomi
authors: Hiroki
authors: H
authors: Murai
authors: Yusei
authors: Y
authors: Ohshima
mesh_terms: D000199:Actins / Q000096:biosynthesis; D001249:Asthma / Q000276:immunology; D001761:Bleomycin; D019013:CD40 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D019013:CD40 Antigens; D020381:Interleukin-17; D015850:Interleukin-6; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D001761:Bleomycin; D003094:Collagen; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
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