The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

Anna Chuprin; Ayelet Avin; Yael Goldfarb; Yonatan Herzig; Ben Levi; Adi Jacob; Asaf Sela; Shir Katz; Moran Grossman; Clotilde Guyon; Moran Rathaus; Haim Y. Cohen; Irit Sagi; Matthieu Giraud; Michael W. McBurney; Eystein S. Husebye; Jakub Abramson

doi:10.1038/ni.3194

The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

Anna Chuprin
, Ayelet Avin
, Yael Goldfarb
, Yonatan Herzig
, Ben Levi
, Adi Jacob
, Asaf Sela
, Shir Katz
, Moran Grossman
, Clotilde Guyon
, Moran Rathaus
, Haim Y. Cohen
, Irit Sagi
, Matthieu Giraud
, Michael W. McBurney
, Eystein S. Husebye
, Jakub Abramson

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

Aire is a transcriptional regulator that induces the promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for the induction of immunological self-tolerance. Studies have offered molecular insights into how Aire operates, but more comprehensive understanding of this process still remains elusive. Here we found abundant expression of the protein deacetylase Sirtuin-1 (Sirt1) in mature Aire + mTECs, wherein it was required for the expression of Aire-dependent TRA-encoding genes and the subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and identifies a unique function for Sirt1 in preventing organ-specific autoimmunity.

Original language	English
Pages (from-to)	737-745
Number of pages	9
Journal	Nature Immunology
Volume	16
Issue number	7
DOIs	https://doi.org/10.1038/ni.3194
State	Published - 20 Jul 2015
Externally published	Yes

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Chuprin, A., Avin, A., Goldfarb, Y., Herzig, Y., Levi, B., Jacob, A., Sela, A., Katz, S., Grossman, M., Guyon, C., Rathaus, M., Cohen, H. Y., Sagi, I., Giraud, M., McBurney, M. W., Husebye, E. S., & Abramson, J. (2015). The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nature Immunology, 16(7), 737-745. https://doi.org/10.1038/ni.3194

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title = "The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance",

abstract = "Aire is a transcriptional regulator that induces the promiscuous expression of thousands of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs), a step critical for the induction of immunological self-tolerance. Studies have offered molecular insights into how Aire operates, but more comprehensive understanding of this process still remains elusive. Here we found abundant expression of the protein deacetylase Sirtuin-1 (Sirt1) in mature Aire + mTECs, wherein it was required for the expression of Aire-dependent TRA-encoding genes and the subsequent induction of immunological self-tolerance. Our study elucidates a previously unknown molecular mechanism for Aire-mediated transcriptional regulation and identifies a unique function for Sirt1 in preventing organ-specific autoimmunity.",

author = "Anna Chuprin and Ayelet Avin and Yael Goldfarb and Yonatan Herzig and Ben Levi and Adi Jacob and Asaf Sela and Shir Katz and Moran Grossman and Clotilde Guyon and Moran Rathaus and Cohen, \{Haim Y.\} and Irit Sagi and Matthieu Giraud and McBurney, \{Michael W.\} and Husebye, \{Eystein S.\} and Jakub Abramson",

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Chuprin, A, Avin, A, Goldfarb, Y, Herzig, Y, Levi, B, Jacob, A, Sela, A, Katz, S, Grossman, M, Guyon, C, Rathaus, M, Cohen, HY, Sagi, I, Giraud, M, McBurney, MW, Husebye, ES & Abramson, J 2015, 'The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance', Nature Immunology, vol. 16, no. 7, pp. 737-745. https://doi.org/10.1038/ni.3194

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AU - Jacob, Adi

AU - Sela, Asaf

AU - Katz, Shir

AU - Grossman, Moran

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AU - Rathaus, Moran

AU - Cohen, Haim Y.

AU - Sagi, Irit

AU - Giraud, Matthieu

AU - McBurney, Michael W.

AU - Husebye, Eystein S.

AU - Abramson, Jakub

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The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance

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