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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proinsulin is encoded by an RNA splice variant in human blood myeloid cells
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Proinsulin is encoded by an RNA splice variant in human blood myeloid cells

机译：胰岛素原是由人血髓样细胞中的RNA剪接变体编码

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摘要

Genes for peripheral tissue-restricted self-antigens are expressed in thymic and hematopoietic cells. In thymic medullary epithelial cells, self-antigen expression imposes selection on developing autoreactive T cells and regulates susceptibility to autoimmune disease in mouse models. Less is known about the role of self-antigen expression by hematopoietic cells. Here we demonstrate that one of the endocrine self-antigens expressed by human blood myeloid cells, proinsulin, is encoded by an RNA splice variant. The surface expression of immunoreactive proinsulin was significantly decreased after transfection of monocytes with small interfering RNA to proinsulin. Furthermore, analogous to proinsulin transcripts in the thymus, the abundance of the proinsulin RNA splice variant in blood cells corresponded with the length of the variable number of tandem repeats 5' of the proinsulin gene, known to be associated with type 1 diabetes susceptibility. Self-antigen expression by peripheral myeloid cells extends the umbrella of "immunological self" and, by analogy with the thymus, may be implicated in peripheral immune tolerance.
机译：外周组织限制性自身抗原的基因在胸腺和造血细胞中表达。在胸腺髓质上皮细胞中，自身抗原表达对正在发育的自身反应性T细胞施加选择，并调节小鼠模型中自身免疫性疾病的易感性。关于造血细胞自身抗原表达的作用知之甚少。在这里，我们证明了人类血液髓样细胞表达的一种内分泌自身抗原，即胰岛素原，是由RNA剪接变体编码的。带有小干扰RNA的单核细胞转染胰岛素原后，免疫反应性胰岛素原的表面表达显着降低。此外，类似于胸腺中的胰岛素原转录物，血细胞中胰岛素原RNA剪接变体的丰度对应于胰岛素原基因的可变数目的串联重复序列5'的长度，已知与1型糖尿病易感性有关。外周髓细胞的自身抗原表达扩展了“免疫学自我”的保护范围，并且与胸腺类似，可能与外周免疫耐受有关。

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