title: Potential role of myeloid cell/eosinophil-derived IL-17 in LPS-induced endotoxin shock.
abstract: IL-17RA is a shared receptor subunit for several cytokines of the IL-17 family, including IL-17A, IL-17C, IL-17E (also called IL-25) and IL-17F. It has been shown that mice deficient in IL-17RA are more susceptible to sepsis than wild-type mice, suggesting that IL-17RA is important for host defense against sepsis. However, it is unclear which ligands for IL-17RA, such as IL-17A, IL-17C, IL-17E/IL-25 and/or IL-17F, are involved in the pathogenesis of sepsis. Therefore, we examined IL-17A, IL-17E/IL-25 and IL-17F for possible involvement in LPS-induced endotoxin shock. IL-17A-deficient mice, but not IL-25- or IL-17F-deficient mice, were resistant to LPS-induced endotoxin shock, as compared with wild-type mice. Nevertheless, studies using IL-6-deficient, IL-21Rα-deficient and Rag-2-deficient mice, revealed that neither IL-6 and IL-21, both of which are important for Th17 cell differentiation, nor Th17 cells were essential for the development of LPS-induced endotoxin shock, suggesting that IL-17A-producing cells other than Th17 cells were important in the setting. In this connection, IL-17A was produced by macrophages, DCs and eosinophils after LPS injection. Taken together, these findings indicate that IL-17A, but not IL-17F or IL-25, is crucial for LPS-induced endotoxin shock. In addition, macrophages, DCs and eosinophils, but not Th17 cells or γδ T cells, may be sources of IL-17A during LPS-induced endotoxin shock.
authors.affiliation: Atopy Research Center, Juntendo University, Tokyo 113-8412, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Shimura
authors.affiliation: Department of Medical Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shibui
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Narushima
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Nambu
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Division of Experimental Animal Immunology, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Akitsu
authors.affiliation: Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.affiliation: Division of Experimental Animal Immunology, Tokyo University of Science, Chiba 278-8510, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Atopy Research Center, Juntendo University, Tokyo 113-8412, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.affiliation: Atopy Research Center, Juntendo University, Tokyo 113-8412, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Animal Research Center, Tokyo Medical University, Tokyo 160-8402, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama 332-0012, Japan. Electronic address: snakae@ims.u-tokyo.ac.jp.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
mesh_terms: D000818:Animals; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D053738:Interleukin-21 Receptor alpha Subunit / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology*; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D012772:Shock, Septic / Q000209:etiology / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology
chemical_list: C098680:Il17a protein, mouse; C515932:Il17f protein, mouse; C491673:Il17ra protein, mouse; C508118:Il21r protein, mouse; D020381:Interleukin-17; D053738:Interleukin-21 Receptor alpha Subunit; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; C442281:Mydgf protein, mouse; D053722:Receptors, Interleukin-17
keywords: IL-17A; IL-17F; IL-25; Sepsis