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

פרסום מחקרי: פרסום בכתב עת › מאמר › ביקורת עמיתים

72 ציטוטים ‏(Scopus)

תקציר

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.

שפה מקורית	אנגלית
עמודים (מ-עד)	737-745
מספר עמודים	9
כתב עת	Nature Immunology
כרך	16
מספר גיליון	7
מזהי עצם דיגיטלי (DOIs)	https://doi.org/10.1038/ni.3194
סטטוס פרסום	פורסם - 20 יולי 2015
פורסם באופן חיצוני	כן

גישה למסמך

10.1038/ni.3194

קבצים וקישורים אחרים

Link to publication in Scopus

פורמט ציטוט ביבליוגרפי

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",

year = "2015",

month = jul,

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doi = "10.1038/ni.3194",

language = "אנגלית",

volume = "16",

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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, כרך 16, מס' 7, עמודים 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

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