| First Author | Tanaka S | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 8 | Pages | 950-961 |
| PubMed ID | 32572241 | Mgi Jnum | J:297806 |
| Mgi Id | MGI:6479286 | Doi | 10.1038/s41590-020-0700-y |
| Citation | Tanaka S, et al. (2020) Tet2 and Tet3 in B cells are required to repress CD86 and prevent autoimmunity. Nat Immunol 21(8):950-961 |
| abstractText | 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. |
