ArticleProceedings of the National Academy of Sciences of the United States of America2006
Proinsulin is encoded by an RNA splice variant in human blood myeloid cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 13 citations in OpenAlex.
- Trial
- The dark side of insulin: A primary autoantigen and instrument of self-destruction in type 1 diabetes.Molecular metabolism · 2021Review
- Emerging roles of hematopoietic cells in the pathobiology of diabetic complications.Trends in endocrinology and metabolism: TEM · 2014Review
- Self-antigen expression in the peripheral immune system: roles in self-tolerance and type 1 diabetes pathogenesis.Current diabetes reports · 2014Review
- Antigen-based vaccination and prevention of type 1 diabetes.Current diabetes reports · 2013Review
- Expression and function of the autoimmune regulator (Aire) gene in non-thymic tissue.Clinical and experimental immunology · 2011Review
- Insulin2 gene (Ins2) transcription by NOD bone marrow-derived cells does not influence autoimmune diabetes development in NOD-Ins2 knockout mice.Scandinavian journal of immunology · 2009Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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