Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity
A contribution of epigenetic modifications to B cell tolerance has been proposed but not directly tested. Here we report that deficiency of ten-eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. Mechanistically, in the absence of Tet2 and Tet3, downregulation of CD86, which normally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take place. The importance of dysregulated CD86 expression in Tet2- and Tet3-deficient B cells was further demonstrated by the restriction, albeit not complete, on aberrant T and B cell activation following anti-CD86 blockade. Tet2- and Tet3-deficient B cells had decreased accumulation of histone deacetylase 1 (HDAC1) and HDAC2 at the Cd86 locus. Thus, our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
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| Enthalten in: |
Nature immunology - 21(2020), 8 vom: 22. Aug., Seite 950-961 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tanaka, Shinya [VerfasserIn] |
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| Links: |
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| Themen: |
B7-2 Antigen |
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| Anmerkungen: |
Date Completed 04.11.2020 Date Revised 18.10.2021 published: Print-Electronic ErratumIn: Nat Immunol. 2020 Sep 21;:. - PMID 32958930 Citation Status MEDLINE |
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| doi: |
10.1038/s41590-020-0700-y |
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| funding: |
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| PPN (Katalog-ID): |
NLM311507891 |
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| 245 | 1 | 0 | |a Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity |
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| 500 | |a ErratumIn: Nat Immunol. 2020 Sep 21;:. - PMID 32958930 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A contribution of epigenetic modifications to B cell tolerance has been proposed but not directly tested. Here we report that deficiency of ten-eleven translocation (Tet) DNA demethylase family members Tet2 and Tet3 in B cells led to hyperactivation of B and T cells, autoantibody production and lupus-like disease in mice. Mechanistically, in the absence of Tet2 and Tet3, downregulation of CD86, which normally occurs following chronic exposure of self-reactive B cells to self-antigen, did not take place. The importance of dysregulated CD86 expression in Tet2- and Tet3-deficient B cells was further demonstrated by the restriction, albeit not complete, on aberrant T and B cell activation following anti-CD86 blockade. Tet2- and Tet3-deficient B cells had decreased accumulation of histone deacetylase 1 (HDAC1) and HDAC2 at the Cd86 locus. Thus, our findings suggest that Tet2- and Tet3-mediated chromatin modification participates in repression of CD86 on chronically stimulated self-reactive B cells, which contributes, at least in part, to preventing autoimmunity | ||
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