Gut memories do not fade: epigenetic regulation of lasting gut homing receptor expression in CD4(+) memory T cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsSzilagyi, B A
de Almeida, M
Polansky, J K
MetadataShow full item record
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.
CitationGut memories do not fade: epigenetic regulation of lasting gut homing receptor expression in CD4(+) memory T cells. 2017, 10 (6):1443-1454 Mucosal Immunol
AffiliationHelmholtz-Zentrum für Infektionsforschhung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit.
- Authors: DeNucci CC, Pagán AJ, Mitchell JS, Shimizu Y
- Issue date: 2010 Mar 1
- Expression of mucosal homing receptor alpha4beta7 by circulating CD4+ cells with memory for intestinal rotavirus.
- Authors: Rott LS, Rosé JR, Bass D, Williams MB, Greenberg HB, Butcher EC
- Issue date: 1997 Sep 1
- Gut homing receptors on CD8 T cells are retinoic acid dependent and not maintained by liver dendritic or stellate cells.
- Authors: Eksteen B, Mora JR, Haughton EL, Henderson NC, Lee-Turner L, Villablanca EJ, Curbishley SM, Aspinall AI, von Andrian UH, Adams DH
- Issue date: 2009 Jul
- α<sub>4</sub>β<sub>7</sub><sup>+</sup> CD4<sup>+</sup> Effector/Effector Memory T Cells Differentiate into Productively and Latently Infected Central Memory T Cells by Transforming Growth Factor β1 during HIV-1 Infection.
- Authors: Cheung KW, Wu T, Ho SF, Wong YC, Liu L, Wang H, Chen Z
- Issue date: 2018 Apr 15
- Adjuvant selection regulates gut migration and phenotypic diversity of antigen-specific CD4<sup>+</sup> T cells following parenteral immunization.
- Authors: Frederick DR, Goggins JA, Sabbagh LM, Freytag LC, Clements JD, McLachlan JB
- Issue date: 2018 Mar