Epithelial-specific Blockage of the Myd88-dependent Tlr Signaling Pathway Contributes to Spontaneous Intestinal Inflammation
نویسندگان
چکیده
s of the 3rd ECCO Congress, Lyon, France, February 28–March 1, 2008 79 Results: A significant differential expression of genes is found comparing Treg from HC to aCD (69 genes, 39 up-, 30 down-regulated) and HC to iCD (52 genes, 25 up-, 27 down-regulated). In both groups, 10 genes were upregulated more than 5fold. Transcripts for CCR4 were among the strongest expressed and showed an up-regulation of 5,0fold (HC vs aCD) and 6,4fold (HC vs iCD), respectively. FACS analysis showed that Treg express the highest level of CCR4 in peripheral T cells. In addition, migration studies showed that Treg migrate preferentially towards TARC the ligand for CCR4. No significant difference in the percentage of CCR4+ Treg comparing HC to CD (57.9±11.3 vs. 54.4±12.7) could be detected, but comparison of normalized mean fluorescence intensity (MFI CCR4+/MFI CCR4-) showed a significant decrease in CD (15.8±3.7 vs 10.4±3.4; p=0.019). Immunohistochemistry showed a significant reduction of CCR4-expressing Treg in CD compared to DIV (44.4% ± 3.9 vs 29.0%±8.0%; p=0.019). Conclusions: CCR4 is a possible target gene for Treg pathobiology in CD. Since TARC is abundantly expressed in diseased mucosa, the decreased expression of CCR4 points to an impaired mucosal Treg migration. Therefore, the migration capacity of Treg in CD is currently under investigation. P252 EPITHELIAL-SPECIFIC BLOCKAGE OF THE MYD88-DEPENDENT TLR SIGNALING PATHWAY CONTRIBUTES TO SPONTANEOUS INTESTINAL
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