Please use this identifier to cite or link to this item: doi:10.22028/D291-29440
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Title: Gut memories do not fade : epigenetic regulation of lasting gut homing receptor expression in CD4+ memory T cells
Author(s): Szilagyi, B. A.
Triebus, J.
Kressler, C.
de Almeida, M.
Tierling, Sascha
Durek, P.
Mardahl, M.
Szilagyi, A.
Floess, S.
Huehn, J.
Syrbe, U.
Walter, J.
Polansky, J. K.
Hamann, A.
Language: English
Title: Mucosal immunology
Volume: 10
Issue: 6
Startpage: 1443
Endpage: 1454
Publisher/Platform: Nature
Year of Publication: 2017
Publikation type: Journal Article
Abstract: The 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.
DOI of the first publication: 10.1038/mi.2017.7
Link to this record: hdl:20.500.11880/27895
ISSN: 1933-0219
Date of registration: 25-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Biowissenschaften
Professorship: NT - Prof. Dr. Jörn Walter
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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