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dc.contributor.authorSzilagyi, B Aen
dc.contributor.authorTriebus, Jen
dc.contributor.authorKressler, Cen
dc.contributor.authorde Almeida, Men
dc.contributor.authorTierling, Sen
dc.contributor.authorDurek, Pen
dc.contributor.authorMardahl, Men
dc.contributor.authorSzilagyi, Aen
dc.contributor.authorFloess, Sen
dc.contributor.authorHuehn, Jen
dc.contributor.authorSyrbe, Uen
dc.contributor.authorWalter, Jen
dc.contributor.authorPolansky, J Ken
dc.contributor.authorHamann, Aen
dc.date.accessioned2017-11-21T14:18:04Z
dc.date.available2017-11-21T14:18:04Z
dc.date.issued2017-11
dc.identifier.citationGut memories do not fade: epigenetic regulation of lasting gut homing receptor expression in CD4(+) memory T cells. 2017, 10 (6):1443-1454 Mucosal Immunolen
dc.identifier.issn1935-3456
dc.identifier.pmid28198363
dc.identifier.doi10.1038/mi.2017.7
dc.identifier.urihttp://hdl.handle.net/10033/621181
dc.description.abstractThe concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments. Repetitive rounds of RA treatment enhanced the stability of de novo induced α4β7. A novel enhancer element in the murine Itga4 locus was identified that showed, correlating to stability, selective DNA demethylation in mucosa-seeking memory cells and methylation-dependent transcriptional activity in a reporter gene assay. This implies that epigenetic mechanisms contribute to the stabilization of α4β7 expression. Analogous DNA methylation patterns could be observed in the human ITGA4 locus, suggesting that its epigenetic regulation is conserved between mice and men. These data prove that mucosa-specific homing mediated by α4β7 is imprinted in CD4(+) memory T cells, reinstating the validity of the concept of "topographical memory" for mucosal tissues, and imply a critical role of epigenetic mechanisms.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleGut memories do not fade: epigenetic regulation of lasting gut homing receptor expression in CD4(+) memory T cells.en
dc.typeArticleen
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschhung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalMucosal immunologyen
refterms.dateFOA2018-05-01T00:00:00Z
html.description.abstractThe concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments. Repetitive rounds of RA treatment enhanced the stability of de novo induced α4β7. A novel enhancer element in the murine Itga4 locus was identified that showed, correlating to stability, selective DNA demethylation in mucosa-seeking memory cells and methylation-dependent transcriptional activity in a reporter gene assay. This implies that epigenetic mechanisms contribute to the stabilization of α4β7 expression. Analogous DNA methylation patterns could be observed in the human ITGA4 locus, suggesting that its epigenetic regulation is conserved between mice and men. These data prove that mucosa-specific homing mediated by α4β7 is imprinted in CD4(+) memory T cells, reinstating the validity of the concept of "topographical memory" for mucosal tissues, and imply a critical role of epigenetic mechanisms.


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