| First Author | Grupillo M | Year | 2012 |
| Journal | Cell Immunol | Volume | 273 |
| Issue | 2 | Pages | 115-23 |
| PubMed ID | 22297234 | Mgi Jnum | J:181355 |
| Mgi Id | MGI:5311079 | Doi | 10.1016/j.cellimm.2011.12.010 |
| Citation | Grupillo M, et al. (2012) Essential roles of insulin expression in Aire(+) tolerogenic dendritic cells in maintaining peripheral self-tolerance of islet beta-cells. Cell Immunol 273(2):115-23 |
| abstractText | Anti-insulin autoimmunity is one of the primary forces in initiating and progressing beta-cell destruction in type 1 diabetes. While insulin expression in thymic medullary epithelial cells has been shown to be essential for establishing beta-cell central tolerance, the function of insulin expression in antigen-presenting cells (APCs) of hematopoietic lineage remains elusive. With a Cre-lox reporter approach, we labeled Aire-expressing cells with enhanced yellow fluorescent proteins, and found that insulin expression in the spleen was restricted predominantly to a population of Aire(+)CD11c(int)B220(+) dendritic cells (DCs). Targeted insulin deletion in APCs failed to induce anti-islet autoimmunity in B6 mice. In contrast, elevated levels of T cell infiltration into islets were observed in B6(g7) congenic mice when insulin was specifically deleted in their CD11c-expressing DCs (B6(g7).CD11c-DeltaIns mice). Thus, insulin expression in BM-derived, Aire(+) tolerogenic DCs may play an essential role to prevent the activation and expansion of insulin-reactive T cells in the periphery. |
