Proinsulin is encoded by an RNA splice variant in human blood myeloid cells
- Author(s)
- Narendran, P; Neale, AM; Lee, BH; Ngui, K; Steptoe, RJ; Morahan, G; Madsen, O; Dromey, JA; Jensen, KP; Harrison, LC;
- Details
- Publication Year 2006-10-31,Volume 103,Issue #44,Page 16430-16435
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- 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.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- THYMIC EPITHELIAL-CELLS; HUMAN T-CELLS; LYMPHOID ORGANS; DENDRITIC CELLS; INSULIN GENE; HEMATOPOIETIC PROGENITORS; IDDM2 LOCUS; EXPRESSION; EPITOPE; AUTOANTIGEN
- Publisher's Version
- https://doi.org/10.1073/pnas.0607380103
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-10-31 12:00:00