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T Cell-Mediated Modulation of Mast Cell Function: Heterotypic Adhesion-Induced Stimulatory or Inhibitory Effects

机译:T细胞介导的肥大细胞功能调节:异型粘附诱导的刺激或抑制作用。

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摘要

Close physical proximity between mast cells and T cells has been demonstrated in several T cell mediated inflammatory processes such as rheumatoid arthritis and sarcoidosis. However, the way by which mast cells are activated in these T cell-mediated immune responses has not been fully elucidated. We have identified and characterized a novel mast cell activation pathway initiated by physical contact with activated T cells, and showed that this pathway is associated with degranulation and cytokine release. The signaling events associated with this pathway of mast cell activation have also been elucidated confirming the activation of the Ras mitogen-activated protein kinase systems. More recently, we hypothesized and demonstrated that mast cells may also be activated by microparticles released from activated T cells that are considered as miniature version of a cell. By extension, microparticles might affect the activity of mast cells, which are usually not in direct contact with T cells at the inflammatory site. Recent works have also focused on the effects of regulatory T cells (Treg) on mast cells. These reports highlighted the importance of the cytokines IL-2 and IL-9, produced by mast cells and T cells, respectively, in obtaining optimal immune suppression. Finally, physical contact, associated by OX40–OX40L engagement has been found to underlie the down-regulatory effects exerted by Treg on mast cell function.
机译:肥大细胞与T细胞之间的物理接近性已在几种T细胞介导的炎症过程(如类风湿性关节炎和结节病)中得到证实。但是,尚未完全阐明在这些T细胞介导的免疫反应中激活肥大细胞的方式。我们已经鉴定和表征了一种新的肥大细胞活化途径,该途径是通过与活化的T细胞物理接触而引发的,并且表明该途径与脱粒和细胞因子释放有关。还已经阐明了与肥大细胞激活的这种途径相关的信号传导事件,从而证实了Ras丝裂原激活的蛋白激酶系统的激活。最近,我们假设并证明肥大细胞也可能被从活化T细胞释放的微粒所活化,这被认为是细胞的微型版本。通过扩展,微粒可能影响肥大细胞的活性,肥大细胞通常不与T细胞在炎症部位直接接触。最近的工作还集中于调节性T细胞(Treg)对肥大细胞的作用。这些报告强调了肥大细胞和T细胞分别产生的细胞因子IL-2和IL-9在获得最佳免疫抑制中的重要性。最后,发现由OX40–OX40L参与而引起的身体接触是Treg对肥大细胞功能的下调作用的基础。

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