肺部一种细胞有“双刃剑”作用

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作者：Kiyoshi Takatsu 来源：《免疫学期刊》 发布时间：2012-2-3
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$ _1 v6 P5 P- u: o日本一个研究小组在利用小鼠进行的实验中发现，肺部大量存在的一种细胞，在持续产生导致过敏症的蛋白质的同时，也具备遏制癌细胞转移的作用。
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3 F! H1 B) w; w富山大学研究生院等机构的研究人员日前在《免疫学期刊》上报告说，如果能够弄清这种细胞的“双刃剑”机制，并且加以利用，人们就能更好地治疗过敏症和癌症。
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医学界认为，嗜酸性粒细胞在人体内的增殖和活跃是引发过敏性哮喘和特应症等过敏症的原因之一。此前的研究显示，免疫系统中的淋巴T细胞产生的白介素-5能促使嗜酸性粒细胞活跃。
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而在新的实验中，日本研究人员发现，小鼠肺部和肠道存在的一种细胞能比淋巴T细胞产生更多的白介素-5。他们将这种细胞命名为“原始白介素-5产生细胞”。今后如果能够找到遏制这种细胞活动的方法，就有可能开发出治疗过敏性哮喘等过敏症的方法。
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此外，研究人员还发现，如果令小鼠体内不能产生白介素-5，那么这些小鼠与普通小鼠相比，体内癌细胞的转移会更快。他们认为，白介素-5作用于嗜酸性粒细胞，遏制了癌细胞的转移。他们计划与澳大利亚合作推进后续研究。（来源：新华社 蓝建中）   
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Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity, c  ]1 e% F0 O5 d" }  K& N2 ?

% Q! p  u3 H: ?* VMasashi Ikutani*,1, Tsutomu Yanagibashi*,1, Masaru Ogasawara*,†, Koichi Tsuneyama‡, Seiji Yamamoto§, Yuichi Hattori§, Taku Kouro¶, Atsuko Itakura‖, Yoshinori Nagai*, Satoshi Takaki# and Kiyoshi Takatsu*,†
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Abstract8 ^) c& h. l2 x8 H
IL-5 is involved in a number of immune responses such as helminth infection and allergy. IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal IgA production. However, the identity of IL-5–producing cells has not been unambiguously characterized. In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5–producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5–producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung tumor metastasis and showed that innate IL-5–producing cells were increased in response to tumor invasion, and their regulation of eosinophils is critical to suppress tumor metastasis. Genetic blockade or neutralization of IL-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis. Conversely, exogenous IL-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5–producing cells thus play a role in tumor surveillance through lung eosinophils and may contribute to development of novel immunotherapies for cancer. ) P9 f9 G; K; R  d7 X0 U% `( A
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Footnotes
) ^3 N7 G8 _9 B3 ?4 f5 \" L↵1 M.I. and T.Y. equally contributed to this work. * U' c4 |: s) p- Q# I
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and by the Ministry of Education, Culture, Sports, Science and Technology Regional Innovation Cluster Program, Toyama/Ishikawa Region, Hokuriku Innovation Cluster for Health Science, Japan. & O* y: b. W' s, ~
The online version of this article contains supplemental material.
7 e: `; e, [% Q. t6 OAbbreviations used in this article: 1 c8 u% i" P+ n! G9 U

2 y( N" }, X- U- E! YESembryonic stemHPFhigh-power fieldIL-5+/VIL-5+/VenusKIknockinKOknockoutLPlamina propriaMLNmesenteric lymph nodePPPeyer’s patchWTwild-type.
) f- h3 e1 V2 v" W( R) xReceived May 2, 2011. 6 o8 @( b! j' D' i  Q5 n
Accepted November 13, 2011.
7 L9 _) T$ _7 a/ D7 M- G/ [Copyright © 2012 by The American Association of Immunologists, Inc.
4 c5 g+ m7 V. lhttp://www.jimmunol.org/content/ ... 5-b8d6-34823d27136d