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  Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3

Rauch, K. S., Hils, M., Lupar, E., Minguet, S., Sigvardsson, M., Rottenberg, M. E., et al. (2016). Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3. Cell Reports, 17, 2827-2836. doi:dx.doi.org/10.1016/j.celrep.2016.11.045.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-B175-C Version Permalink: https://hdl.handle.net/21.11116/0000-0008-9AEC-1
Genre: Journal Article

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https://www.sciencedirect.com/science/article/pii/S2211124716316187?via%3Dihub (Publisher version)
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 Creators:
Rauch, Katharina S.1, Author
Hils, Miriam1, Author
Lupar, Ekaterina1, Author
Minguet, Susana1, Author
Sigvardsson, Mikael1, Author
Rottenberg, Martin E.1, Author
Izcue, Ana2, Author
Schachtrup, Christian1, Author
Schachtrup, Kristina1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 Abstract: The transcription factor Foxp3 dominantly controls regulatory T (Treg) cell function, and only its continuous expression guarantees the maintenance of full Treg cell-suppressive capacity. However, transcriptional regulators maintaining Foxp3 transcription are incompletely described. Here, we report that high E47 transcription factor activity in Treg cells resulted in unstable Foxp3 expression. Under homeostatic conditions, Treg cells expressed high levels of the E47 antagonist Id3, thus restricting E47 activity and maintaining Foxp3 expression. In contrast, stimulation of Id3-deficient or E47-overexpressing Treg cells resulted in the loss of Foxp3 expression in a subset of Treg cells in vivo and in vitro. Mechanistic analysis indicated that E47 activated expression of the transcription factor Spi-B and the suppressor of cytokine signaling 3 (SOCS3), which both downregulated Foxp3 expression. These findings demonstrate that the balance of Id3 and E47 controls the maintenance of Foxp3 expression in Treg cells and, thus, contributes to Treg cell plasticity.

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Language(s): eng - English
 Dates: 2016-12-13
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: dx.doi.org/10.1016/j.celrep.2016.11.045
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Title: Cell Reports
Source Genre: Journal
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Pages: - Volume / Issue: 17 Sequence Number: - Start / End Page: 2827 - 2836 Identifier: Other: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247