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IL-17A/F Modulates Fibrocyte Functions in Cooperation with CD40-Mediated Signaling

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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.

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Acknowledgments

We thank Ms. Yuki Mori for her excellent assistance in carrying out these studies. This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (to Y.O.).

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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida-gun, Fukui, 910-1193, Japan

    Hisako Hayashi, Akiko Kawakita, Shintaro Okazaki, Motoko Yasutomi, Hiroki Murai & Yusei Ohshima

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  1. Hisako Hayashi
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Correspondence to Yusei Ohshima.

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Hayashi, H., Kawakita, A., Okazaki, S. et al. IL-17A/F Modulates Fibrocyte Functions in Cooperation with CD40-Mediated Signaling. Inflammation 36, 830–838 (2013). https://doi.org/10.1007/s10753-013-9609-z

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