Unknown,Transcriptomics,Genomics,Proteomics

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Examination of inflammatory transcripts during a transfer model of type I diabetes.


ABSTRACT: In an accompanying paper we found specific localization of diabetogenic T cells only to islets of Langerhans bearing the specific antigen. Instrumental in the specific localization was the presence of intra-islet dendritic cells bearing the β-cell-peptide-MHC complex. Here we report that the entry of diabetogenic CD4 T cells very rapidly triggered inflammatory gene expression changes in islets and vessels by up-regulating chemokines and adhesion molecules. VCAM-1 expression was notable in blood vessels and so was ICAM-1. ICAM-1 was also found on β-cells. These expression changes induced the entry of non-specific T cells that otherwise did not localize to the islets. In contrast to the entry of diabetogenic CD4 T cells, the entrance of non-specific T cells required a chemokine response and VCAM-1 expression by the islets. Interferon-gamma was important for the early gene expression changes in the islets. By microarray analysis we detected up-regulation of a group of interferon-inducible genes as early as 8 hours post T cell transfer. These studies provide a baseline to examine the development of therapeutics that can modulate islet localization of diabetogenic T cells to control this autoimmune disease. 20 total samples

ORGANISM(S): Mus musculus

SUBMITTER: Emil Unanue 

PROVIDER: E-GEOD-26147 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Entry of diabetogenic T cells into islets induces changes that lead to amplification of the cellular response.

Calderon Boris B   Carrero Javier A JA   Miller Mark J MJ   Unanue Emil R ER  

Proceedings of the National Academy of Sciences of the United States of America 20110110 4


In an accompanying paper, we find specific localization of diabetogenic T cells only to islets of Langerhans bearing the specific antigen. Instrumental in the specific localization was the presence of intraislet dendritic cells bearing the β-cell-peptide-MHC complex. Here, we report that the entry of diabetogenic CD4 T cells very rapidly triggered inflammatory gene expression changes in islets and vessels by up-regulating chemokines and adhesion molecules. Vascular cell adhesion molecule-1 (VCAM  ...[more]

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