Combined stimulation with the T helper cell type 2 cytokines interleukin (IL)-4 and IL-10 induces mouse mast cell apoptosis.-猫眼课题宝

DOI：

10.1084/jem.192.8.1093

发表时间：

2000-10-16

期刊：

The Journal of experimental medicine

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Yeatman CF 2nd;Jacobs-Helber SM;Mirmonsef P;Gillespie SR;Bouton LA;Collins HA;Sawyer ST;Shelburne CP;Ryan JJ

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195863/?report=classic

肥大细胞见于全身的结缔组织和粘膜组织中。它们通过免疫球蛋白E(IgE)与抗原的相互作用在辅助性T细胞2型(Th2)细胞因子的促进下被激活，并导致变态反应性疾病的后遗症。我们现在报道一种Th2细胞因子调节肥大细胞存活的机制。具体地说，我们发现IL-4和IL-10诱导依赖IL-3的骨髓源性肥大细胞和腹膜肥大细胞凋亡。这一过程需要与IL-3、IL-4和IL-10共刺激6d，并表达信号转导和转录激活因子6(Stat6)。细胞凋亡与bclxl、bcl2表达降低有关。虽然这一过程独立于Fas途径发生，但在IL-3+IL-4+IL-10中培养的肥大细胞对Fas介导的死亡具有极大的敏感度。此外，我们还发现，免疫球蛋白E的交叉连接或干细胞因子的刺激增强了IL-4和IL-10的凋亡能力。最后，IL-3非依赖性肥大细胞瘤和肥大细胞株对IL-3+IL-4+IL-10诱导的细胞凋亡具有抵抗作用。这些数据提供了Th2细胞因子介导的动态平衡的证据，通过这些细胞因子可以诱导和限制过敏反应。这一途径的失调可能在变态反应性疾病和肥大细胞瘤的生存中发挥作用。

Mast cells are found in connective and mucosal tissues throughout the body. Their activation via immunoglobulin E (IgE)–antigen interactions is promoted by T helper cell type 2 (Th2) cytokines and leads to the sequelae of allergic disease. We now report a mechanism by which Th2 cytokines can regulate mast cell survival. Specifically, we find that interleukin (IL)-4 and IL-10 induce apoptosis in IL-3–dependent bone marrow–derived mast cells and peritoneal mast cells. This process required 6 d of costimulation with IL-3, IL-4, and IL-10, and expression of signal transducer and activator of transcription 6 (Stat6). Apoptosis was coupled with decreased expression of bcl-xL and bcl-2. While this process occurred independent of the Fas pathway, culture in IL-3+IL-4+IL-10 greatly sensitized mast cells to Fas-mediated death. Additionally, we found that IgE cross-linkage or stimulation with stem cell factor enhanced the apoptotic abilities of IL-4 and IL-10. Finally, IL-3–independent mastocytomas and mast cell lines were resistant to apoptosis induced by IL-3+IL-4+IL-10. These data offer evidence of Th2 cytokine–mediated homeostasis whereby these cytokines both elicit and limit allergic responses. Dysregulation of this pathway may play a role in allergic disease and mast cell tumor survival.