Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298, United States.
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, United States.
Cell Immunol. 2021 Jun;364:104344. doi: 10.1016/j.cellimm.2021.104344. Epub 2021 Mar 18.
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.
肥大细胞主要存在于与外部环境的交界处，在那里它们提供对病原体的保护，但也引发过敏炎症。抗原诱导的 IgE 与高亲和力受体 FcεRI 结合导致的肥大细胞活化是导致炎症和支气管收缩的关键因素。我们之前发现 Stat5 被 FcεRI 激活，Stat5B 抑制减少了体外 IgE 诱导的细胞因子产生，但尚未评估体内反应。我们现在表明，Stat5B 缺陷型 (KO) 小鼠对 IgE 介导的过敏反应的反应降低，尽管肥大细胞组织分布正常。同样，Stat5B KO 肥大细胞的 IgE 诱导脱颗粒和细胞因子分泌减少。这些小鼠的 IgE 产生升高，但与内在 B 细胞缺陷无关。目前的工作表明，Stat5B 同工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。
