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Patients with cystic fibrosis have inducible IL-17<sup>+<\/sup>IL-22<sup>+<\/sup> memory cells in lung draining lymph nodes. <i>J. Allergy Clin. Immunol.<\/i>, <b>131<\/b>, 1117\u20131129.e5 (2013).","DOI":"10.1016\/j.jaci.2012.05.036"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Mizunoe S, Shuto T, Suzuki S, Matsumoto C, Watanabe K, Ueno-Shuto K, Suico MA, Onuki K, Gruenert DC, Kai H. Synergism between interleukin (IL)-17 and Toll-like receptor 2 and 4 signals to induce IL-8 expression in cystic fibrosis airway epithelial cells. <i>J. Pharmacol. Sci.<\/i>, <b>118<\/b>, 512\u2013520 (2012).","DOI":"10.1254\/jphs.11240FP"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Gaffen SL. Structure and signalling in the IL-17 receptor family. <i>Nat. Rev. Immunol.<\/i>, <b>9<\/b>, 556\u2013567 (2009).","DOI":"10.1038\/nri2586"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Pappu R, Rutz S, Ouyang W. Regulation of epithelial immunity by IL-17 family cytokines. <i>Trends Immunol.<\/i>, <b>33<\/b>, 343\u2013349 (2012).","DOI":"10.1016\/j.it.2012.02.008"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Ramirez-Carrozzi V, Sambandam A, Luis E, <i>et al<\/i>. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. <i>Nat. Immunol.<\/i>, <b>12<\/b>, 1159\u20131166 (2011).","DOI":"10.1038\/ni.2156"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Song X, Zhu S, Shi P, Liu Y, Shi Y, Levin SD, Qian Y. IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. <i>Nat. Immunol.<\/i>, <b>12<\/b>, 1151\u20131158 (2011).","DOI":"10.1038\/ni.2155"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Johansen C, Riis JL, Gedebjerg A, Kragballe K, Iversen L. Tumor necrosis factor \u03b1-mediated induction of interleukin 17C in human keratinocytes is controlled by nuclear factor \u03baB. <i>J. Biol. Chem.<\/i>, <b>286<\/b>, 25487\u201325494 (2011).","DOI":"10.1074\/jbc.M111.240671"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Pfeifer P, Voss M, Wonnenberg B, Hellberg J, Seiler F, Lepper PM, Bischoff M, Langer F, Sch\u00e4fers H-J, Menger MD, Bals R, Beisswenger C. IL-17C is a mediator of respiratory epithelial innate immune response. <i>Am. J. Respir. Cell Mol. Biol.<\/i>, <b>48<\/b>, 415\u2013421 (2013).","DOI":"10.1165\/rcmb.2012-0232OC"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Kusagaya H, Fujisawa T, Yamanaka K, Mori K, Hashimoto D, Enomoto N, Inui N, Nakamura Y, Wu R, Maekawa M, Suda T, Chida K. Toll-like receptor-mediated airway IL-17C enhances epithelial host defense in an autocrine\/paracrine manner. <i>Am. J. Respir. Cell Mol. 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