| Essential roles of insulin expression in Aire(+) tolerogenic dendritic cells in maintaining peripheral self-tolerance of islet β-cells. | |
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MedLine Citation:
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PMID: 22297234 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Anti-insulin autoimmunity is one of the primary forces in initiating and progressing β-cell destruction in type 1 diabetes. While insulin expression in thymic medullary epithelial cells has been shown to be essential for establishing β-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-ΔIns 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. |
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Authors:
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Maria Grupillo; Giulio Gualtierotti; Jing He; Giorgia Sisino; Rita Bottino; William A Rudert; Massimo Trucco; Yong Fan |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-12 |
Journal Detail:
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Title: Cellular immunology Volume: - ISSN: 1090-2163 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-2-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1246405 Medline TA: Cell Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Immunogenetics, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Ri.Med Foundation, Palermo, Italy; Science of Transplantation, Pisa University, Pisa, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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