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Regulation of inflammatory responses by IL-17F

Regulation of inflammatory responses by IL-17F Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases. Footnotes Abbreviations used: BALF, bronchoalveolar lavage fluid; CC10, Clara cell 10; CNS, central nervous system; DSS, dextran sulfate sodium; EAE, experimental autoimmune encephalomyelitis; FAP, allergenic fungal proteinase; H&E, hematoxylin and eosin; MEF, mouse embryonic fibroblast; MMP, matrix metalloproteinase; MOG, myelin oligodendrocyte glycoprotein; PAS, periodic acid Schiff; TRAF6, TNFR-associated factor 6. X.O. Yang and S.H. Chang contributed equally to this study. © 2008 Yang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ). Submitted: 13 September 2007 Accepted: 18 March 2008 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Experimental Medicine Rockefeller University Press

Regulation of inflammatory responses by IL-17F

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References (51)

Publisher
Rockefeller University Press
Copyright
© 2008 Yang et al.
ISSN
0022-1007
eISSN
1540-9538
DOI
10.1084/jem.20071978
pmid
18411338
Publisher site
See Article on Publisher Site

Abstract

Although interleukin (IL) 17 has been extensively characterized, the function of IL-17F, which has an expression pattern regulated similarly to IL-17, is poorly understood. We show that like IL-17, IL-17F regulates proinflammatory gene expression in vitro, and this requires IL-17 receptor A, tumor necrosis factor receptor–associated factor 6, and Act1. In vivo, overexpression of IL-17F in lung epithelium led to infiltration of lymphocytes and macrophages and mucus hyperplasia, similar to observations made in IL-17 transgenic mice. To further understand the function of IL-17F, we generated and analyzed mice deficient in IL-17F or IL-17. IL-17, but not IL-17F, was required for the initiation of experimental autoimmune encephalomyelitis. Mice deficient in IL-17F, but not IL-17, had defective airway neutrophilia in response to allergen challenge. Moreover, in an asthma model, although IL-17 deficiency reduced T helper type 2 responses, IL-17F–deficient mice displayed enhanced type 2 cytokine production and eosinophil function. In addition, IL-17F deficiency resulted in reduced colitis caused by dextran sulfate sodium, whereas IL-17 knockout mice developed more severe disease. Our results thus demonstrate that IL-17F is an important regulator of inflammatory responses that seems to function differently than IL-17 in immune responses and diseases. Footnotes Abbreviations used: BALF, bronchoalveolar lavage fluid; CC10, Clara cell 10; CNS, central nervous system; DSS, dextran sulfate sodium; EAE, experimental autoimmune encephalomyelitis; FAP, allergenic fungal proteinase; H&E, hematoxylin and eosin; MEF, mouse embryonic fibroblast; MMP, matrix metalloproteinase; MOG, myelin oligodendrocyte glycoprotein; PAS, periodic acid Schiff; TRAF6, TNFR-associated factor 6. X.O. Yang and S.H. Chang contributed equally to this study. © 2008 Yang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ). Submitted: 13 September 2007 Accepted: 18 March 2008

Journal

The Journal of Experimental Medicine – Rockefeller University Press

Published: May 12, 2008

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