کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1905974 | 1534751 | 2006 | 9 صفحه PDF | دانلود رایگان |

Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β-cells of the islets of Langerhans. One still open question is where naive islet-reactive T cells encounter antigens and become stimulated. In this report we have re-examined the expression of MHC class II (MHCII) genes in human islets to further explore the possibility that non-professional antigen presenting cells (APCs) within islets contribute to autoimmunity. Since development of T1D has been linked to viral infections, we also studied ex-vivo MHCII expression in response to interferon-α (IFNα) in islet tissue and in different APCs. The findings are: first, MHCII genes expression in human islets is linked with the expression of the class II transactivator isoform transcribed from the promoter IV, similar to that described in non-professional APCs. Second, there is IFNα-mediated lineage-specific regulation of MHCII genes expression, seen as a decrease in the accumulation of MHCII transcripts in pancreatic islets opposite to an increase in dendritic cells and B-lymphoblastoid cell lines. Third, there is allele-specific regulation of the HLA-DQA1 gene by IFNα in islet tissue. These findings may begin to explain the molecular events that create favorable conditions for organ-specific autoimmunity and explain the incomplete penetrance of T1D susceptibility alleles.
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1762, Issue 6, June 2006, Pages 627–635