The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus.
The Role of Dendritic Cell Maturation in the Induction of Insulin-Dependent Diabetes Mellitus.
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DOI：
10.3389/fimmu.2017.00327
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发表时间：
2017
影响因子：
7.3
通讯作者：
Langridge WH
中科院分区：
文献类型：
--
作者：
Mbongue JC;Nieves HA;Torrez TW;Langridge WH
树突状细胞（dc）是人类抗原呈递细胞的主要类别，主要负责启动和引导涉及维持免疫稳态的先天和适应性免疫反应。未成熟的树突状细胞（iDCs）吞噬病原体和有毒蛋白，并在内体囊泡中将它们降解成小片段，然后在主要组织相容性复合体（MHC） II受体分子上呈递给naïve同源T细胞（Th0）。除了在刺激免疫方面的作用外，dc还参与诱导和维持对自身抗原的免疫耐受。在激活过程中，idc逐渐成熟。成熟开始于dc停止吸收抗原，并开始从周围组织的位置迁移到邻近的淋巴结或脾脏，在其持续成熟过程中，dc将储存在MHCII受体分子表面的抗原呈递给幼稚的Th0细胞。在抗原呈递过程中，dc上调质膜上共刺激受体分子CD86、CD80、CD83和CD40的生物合成。这些活化的DC受体分子结合Th0细胞膜上的同源CD28受体，触发DC分泌IL-12或IL-10细胞因子，导致T细胞分化为亲T细胞亚群或抗炎T细胞亚群。虽然iDC激活和Th0细胞分化过程中涉及的基本概念之前已经有文献记载，但它们的定义很差。在这篇综述中，我们详细介绍了DC成熟过程及其在胰岛素依赖型糖尿病自身免疫诱导中的作用。
Dendritic cells (DCs) are the dominant class of antigen-presenting cells in humans and are largely responsible for the initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs) phagocytize pathogens and toxic proteins and in endosomal vesicles degrade them into small fragments for presentation on major histocompatibility complex (MHC) II receptor molecules to naïve cognate T cells (Th0). In addition to their role in stimulation of immunity, DCs are involved in the induction and maintenance of immune tolerance toward self-antigens. During activation, the iDCs become mature. Maturation begins when the DCs cease taking up antigens and begin to migrate from their location in peripheral tissues to adjacent lymph nodes or the spleen where during their continued maturation the DCs present stored antigens on surface MHCII receptor molecules to naive Th0 cells. During antigen presentation, the DCs upregulate the biosynthesis of costimulatory receptor molecules CD86, CD80, CD83, and CD40 on their plasma membrane. These activated DC receptor molecules bind cognate CD28 receptors presented on the Th0 cell membrane, which triggers DC secretion of IL-12 or IL-10 cytokines resulting in T cell differentiation into pro- or anti-inflammatory T cell subsets. Although basic concepts involved in the process of iDC activation and guidance of Th0 cell differentiation have been previously documented, they are poorly defined. In this review, we detail what is known about the process of DC maturation and its role in the induction of insulin-dependent diabetes mellitus autoimmunity.