Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo.

Stat5B is required for IgE-Mediated mast cell function in vitro and in vivo.
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DOI:
10.1016/j.cellimm.2021.104344
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发表时间:
2021-06
影响因子:
4.3
通讯作者:
Ryan JJ
Ryan JJ
中科院分区:
医学4区
文献类型:
--
作者:
Kiwanuka KN;Motunrayo Kolawole E;Mcleod JJA;Baker B;Paez PA;Zellner MP;Haque TT;Paranjape A;Jackson K;Kee SA;Dailey J;Martin RK;Ryan JJ

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肥大细胞主要在与外部环境的交界处被发现,在那里它们提供对病原体的保护,但也会引起过敏性炎症。通过抗原诱导与高亲和力受体FcεRI结合的Ig E聚集而激活的肥大细胞是导致炎症和支气管收缩的关键因素。我们先前发现STAT5被FcεRI激活,并且在体外抑制STAT5B减少了免疫球蛋白E诱导的细胞因子的产生,但在体内的反应尚未得到评估。我们现在发现,尽管肥大细胞组织分布正常,Stat5B缺陷(KO)小鼠对IgE介导的过敏反应的反应减少。类似地,Stat5B KO肥大细胞在体外减少了IgE诱导的脱颗粒和细胞因子的分泌。这些小鼠有升高的IgE产生,这与固有的B细胞缺陷无关。目前的工作表明,Stat5B亚型是正常肥大细胞功能所必需的,并表明它限制了体内IgE的产生。
Mast cells are found primarily at interfaces with the external environment, where they provide protection from pathogens but also elicit allergic inflammation. Mast cell activation by antigen-induced aggregation of IgE bound to the high affinity receptor, FcεRI, is a critical factor leading to inflammation and bronchoconstriction. We previously found that Stat5 is activated by FcεRI and that Stat5B suppression decreased IgE-induced cytokine production in vitro, but in vivo responses have not been assessed. We now show that Stat5B-deficient (KO) mice have reduced responses to IgE-mediated anaphylaxis, despite normal mast cell tissue distribution. Similarly, Stat5B KO mast cells have diminished IgE-induced degranulation and cytokine secretion in vitro. These mice have elevated IgE production that is not correlated with an intrinsic B cell defect. The current work demonstrates that the Stat5B isoform is required for normal mast cell function and suggests it limits IgE production in vivo.
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