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

69 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

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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.",

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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 - Herzig, Yonatan

AU - Levi, Ben

AU - Jacob, Adi

AU - Sela, Asaf

AU - Katz, Shir

AU - Grossman, Moran

AU - Guyon, Clotilde

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

Abstract

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