Potential role of myeloid cell/eosinophil-derived IL-17 in LPS-induced endotoxin shock.
Potential role of myeloid cell/eosinophil-derived IL-17 in LPS-induced endotoxin shock.
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DOI：
10.1016/j.bbrc.2014.09.004
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发表时间：
2014-10-10
影响因子：
3.1
通讯作者：
Nakae, Susumu
中科院分区：
文献类型：
--
作者：
Shimura, Eri;Shibui, Akiko;Narushima, Seiko;Nambu, Aya;Yamaguchi, Sachiko;Akitsu, Aoi;Leonard, Warren J.;Iwakura, Yoichiro;Matsumoto, Kenji;Suto, Hajime;Okumura, Ko;Sudo, Katsuko;Nakae, Susumu
IL-17 RA是IL-17家族的几种细胞因子的共有受体亚基，包括IL-17 A、IL-17 C、IL-17 E（也称为IL-25）和IL-17 F。研究表明，IL-17 RA缺陷的小鼠比野生型小鼠更容易患败血症，这表明IL-17 RA对于宿主防御败血症很重要。然而，目前尚不清楚IL-17 RA的哪些配体，如IL-17 A、IL-17 C、IL-17 E/IL-25和/或IL-17 F参与脓毒症的发病机制。因此，我们检测了IL-17 A、IL-17 E/IL-25和IL-17 F是否可能参与LPS诱导的内毒素休克。与野生型小鼠相比，IL-17 A缺陷型小鼠对LPS诱导的内毒素休克具有抗性，但IL-25或IL-17 F缺陷型小鼠则无此作用。然而，使用IL-6缺陷型、IL-21 R α缺陷型和Rag-2缺陷型小鼠进行的研究显示，IL-6和IL-21（两者对Th 17细胞分化都很重要）以及Th 17细胞对于LPS诱导的内毒素休克的发生都不是必需的，这表明IL-17 A产生细胞而不是Th 17细胞在该环境中是重要的。在这方面，IL-17 A在LPS注射后由巨噬细胞、DC和嗜酸性粒细胞产生。总之，这些发现表明IL-17 A，而不是IL-17 F或IL-25，是LPS诱导的内毒素休克的关键。此外，巨噬细胞、DC和嗜酸性粒细胞可能是LPS诱导的内毒素休克过程中IL-17 A的来源，而不是Th 17细胞或γδ T细胞。
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.
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影响因子：
4.8
作者：
Bosmann, Markus;Patel, Vinay R.;Ward, Peter A.
通讯作者：
Ward, Peter A.
影响因子：
4.8
作者：
Flierl, Michael A.;Rittirsch, Daniel;Ward, Peter A.
通讯作者：
Ward, Peter A.
DOI：
10.1073/pnas.1003988107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Price, April E.;Liang, Hong-Erh;Locksley, Richard M.
通讯作者：
Locksley, Richard M.
影响因子：
4.4
作者：
Freitas, Andressa;Alves-Filho, Jose C.;Ryffel, Bernhard
通讯作者：
Ryffel, Bernhard
影响因子：
3.1
作者：
Bosmann, Markus;Russkamp, Norman F.;Ward, Peter A.
通讯作者：
Ward, Peter A.