miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression.
<h4>Background</h4>In humans and mice naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive...
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oai:doaj.org-article:e9945b4d46fd4efaa142babce00146032021-11-25T06:20:11ZmiR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression.1932-620310.1371/journal.pone.0007158https://doaj.org/article/e9945b4d46fd4efaa142babce00146032009-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19777054/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>In humans and mice naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance.<h4>Principal findings</h4>DNA-Microarray analyses of human as well as murine conventional CD4(+) Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice and performing FoxP3 ChIP-Seq experiments using activated human T lymphocytes, we show that the expression and maturation of miR-155 seem to be not necessarily regulated by FoxP3. In order to address the functional relevance of elevated miR-155 levels, we transfected miR-155 inhibitors or mature miR-155 RNAs into freshly-isolated human and mouse primary CD4(+) Th cells and nTregs and investigated the resulting phenotype in nTreg suppression assays. Whereas miR-155 inhibition in conventional CD4(+) Th cells strengthened nTreg cell-mediated suppression, overexpression of mature miR-155 rendered these cells unresponsive to nTreg cell-mediated suppression.<h4>Conclusion</h4>Investigation of FoxP3 downstream targets, certainly of bound and regulated miRNAs revealed the associated function between the master regulator FoxP3 and miRNAs as regulators itself. miR-155 is shown to be crucially involved in nTreg cell mediated tolerance by regulating the susceptibility of conventional human as well as murine CD4(+) Th cells to nTreg cell-mediated suppression.Heiko F StahlTanja FautiNina UllrichTobias BoppJan KubachWerner RustPaul LabhartVassili AlexiadisChristian BeckerMathias HafnerAndreas WeithMartin C LenterHelmut JonuleitEdgar SchmittDetlev MennerichPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 9, p e7158 (2009) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Heiko F Stahl Tanja Fauti Nina Ullrich Tobias Bopp Jan Kubach Werner Rust Paul Labhart Vassili Alexiadis Christian Becker Mathias Hafner Andreas Weith Martin C Lenter Helmut Jonuleit Edgar Schmitt Detlev Mennerich miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. |
| description |
<h4>Background</h4>In humans and mice naturally occurring CD4(+)CD25(+) regulatory T cells (nTregs) are a thymus-derived subset of T cells, crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Recent work using Dicer-deficient mice irrevocably demonstrated the importance of miRNAs for nTreg cell-mediated tolerance.<h4>Principal findings</h4>DNA-Microarray analyses of human as well as murine conventional CD4(+) Th cells and nTregs revealed a strong up-regulation of mature miR-155 (microRNA-155) upon activation in both populations. Studying miR-155 expression in FoxP3-deficient scurfy mice and performing FoxP3 ChIP-Seq experiments using activated human T lymphocytes, we show that the expression and maturation of miR-155 seem to be not necessarily regulated by FoxP3. In order to address the functional relevance of elevated miR-155 levels, we transfected miR-155 inhibitors or mature miR-155 RNAs into freshly-isolated human and mouse primary CD4(+) Th cells and nTregs and investigated the resulting phenotype in nTreg suppression assays. Whereas miR-155 inhibition in conventional CD4(+) Th cells strengthened nTreg cell-mediated suppression, overexpression of mature miR-155 rendered these cells unresponsive to nTreg cell-mediated suppression.<h4>Conclusion</h4>Investigation of FoxP3 downstream targets, certainly of bound and regulated miRNAs revealed the associated function between the master regulator FoxP3 and miRNAs as regulators itself. miR-155 is shown to be crucially involved in nTreg cell mediated tolerance by regulating the susceptibility of conventional human as well as murine CD4(+) Th cells to nTreg cell-mediated suppression. |
| format |
article |
| author |
Heiko F Stahl Tanja Fauti Nina Ullrich Tobias Bopp Jan Kubach Werner Rust Paul Labhart Vassili Alexiadis Christian Becker Mathias Hafner Andreas Weith Martin C Lenter Helmut Jonuleit Edgar Schmitt Detlev Mennerich |
| author_facet |
Heiko F Stahl Tanja Fauti Nina Ullrich Tobias Bopp Jan Kubach Werner Rust Paul Labhart Vassili Alexiadis Christian Becker Mathias Hafner Andreas Weith Martin C Lenter Helmut Jonuleit Edgar Schmitt Detlev Mennerich |
| author_sort |
Heiko F Stahl |
| title |
miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. |
| title_short |
miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. |
| title_full |
miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. |
| title_fullStr |
miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. |
| title_full_unstemmed |
miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. |
| title_sort |
mir-155 inhibition sensitizes cd4+ th cells for treg mediated suppression. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/e9945b4d46fd4efaa142babce0014603 |
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