Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice
Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice
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DOI：
10.1038/ni768
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发表时间：
2002-03-01
影响因子：
30.5
通讯作者：
Koyasu, S
中科院分区：
文献类型：
--
作者：
Fukao, T;Yamada, T;Koyasu, S
缺乏磷脂酰肌醇-3激酶（PI 3 K）的p85 α调节亚基的小鼠缺乏胃肠和腹膜肥大细胞，但具有真皮肥大细胞。因此，这些小鼠对急性脓毒性腹膜炎表现出受损的细菌清除，并且对肠线虫委内瑞拉圆线虫的感染高度敏感。然而，全身过敏性休克反应完好无损。我们发现，尽管用骨髓来源的肥大细胞（BMMC）重建PI 3 K（-/-）小鼠恢复了抗细菌免疫，但只有T辅助细胞2型（T（H）2）条件化的BMMC，而不是“标准”BMMC，能够恢复抗线虫免疫。这一发现强调了T（H）2反应在控制线虫感染中的重要性。因此，PI 3 K可能通过调节肥大细胞的发育和诱导在宿主免疫应答中起重要作用。
Mice that lack the p85alpha regulatory subunit of phosphatidylinositol-3 kinase (PI3K) are deficient in gastrointestinal and peritoneal mast cells but have dermal mast cells. Accordingly, these mice show impaired bacterial clearance in response to acute septic peritonitis and are highly susceptible to infection by the intestinal nematode Strongyloides venezuelensis. Systemic anaphylactic shock responses, however, are intact. We found that although reconstitution of PI3K(-/-) mice with bone marrow-derived mast cells (BMMCs) restored anti-bacterial immunity, only T helper type 2 (T(H)2)-conditioned BMMCs, not "standard" BMMCs, were able to restore anti-nematode immunity. This finding highlights the importance of the T(H)2 response in the control of nematode infection. Thus, PI3K likely plays an essential role in host immune responses by regulating both the development and induction of mast cells.