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首页> 外文期刊>Journal of neuroendocrinology >Thymic transcription of neurohypophysial and insulin-related genes: impact upon T-cell differentiation and self-tolerance.
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Thymic transcription of neurohypophysial and insulin-related genes: impact upon T-cell differentiation and self-tolerance.

机译:神经垂体和胰岛素相关基因的胸腺转录:对T细胞分化和自我耐受的影响。

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摘要

Abstract The thymus is the unique lymphoid organ responsible for the generation of a diverse repertoire of T lymphocytes that are competent against non self-antigens while being tolerant to self-antigens. A vast repertoire of neuroendocrine-related genes is transcribed in the nonlymphoid cellular compartment of the thymus (thymic epithelial cells, dendritic cells and macrophages). The precursors encoded by these genes engage two types of interactions with developing T cells (thymocytes). First, they are not processed in a classical neuroendocrine way but as the source of self-antigens that are presented to pre-T cells by the major histocompatibility complex proteins of the thymus. This presentation could be responsible for the establishment of central T-cell self-tolerance to neuroendocrine functions. Second, they also deliver signal ligands that are able to bind to neuroendocrine-type receptors expressed by thymocytes. This interaction activates several types of intracellular signalling pathways implicated in the developmental process of T lymphocytes. Several experimental arguments support a role for thymic dysfunction as a crucial factor in the development of organ-specific autoimmune endocrinopathies, such as 'idiopathic' central diabetes insipidus and type 1 diabetes mellitus. The rational use of tolerogenic neuroendocrine self-antigens for the prevention/treatment of autoimmune endocrinopathies is currently under investigation.
机译:摘要胸腺是独特的淋巴器官,负责产生多种T淋巴细胞,这些T淋巴细胞可以抵抗非自身抗原,同时可以耐受自身抗原。在胸腺的非淋巴细胞隔室(胸腺上皮细胞,树突状细胞和巨噬细胞)中转录了大量与神经内分泌相关的基因。这些基因编码的前体与正在发育的T细胞(胸腺细胞)发生两种相互作用。首先,它们不是以经典的神经内分泌方式加工的,而是作为胸腺主要组织相容性复合蛋白呈递给pre-T细胞的自身抗原的来源。该演示文稿可能负责建立对神经内分泌功能的中央T细胞自我耐受。其次,它们还传递能够与胸腺细胞表达的神经内分泌型受体结合的信号配体。这种相互作用激活了涉及T淋巴细胞发育过程的几种类型的细胞内信号通路。几个实验论证支持胸腺功能障碍是器官特异性自身免疫性内分泌病发展的关键因素,例如“特发性”中枢性尿崩症和1型糖尿病。目前正在研究合理使用耐受性神经内分泌自身抗原预防/治疗自身免疫性内分泌病。

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