| First Author | Zheng X | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 11 | Pages | 111114 |
| PubMed ID | 39498302 | Mgi Jnum | J:360989 |
| Mgi Id | MGI:7778991 | Doi | 10.1016/j.isci.2024.111114 |
| Citation | Zheng X, et al. (2024) Inducible deletion of Ezh2 in CD4(+) T cells inhibits kidney T cell infiltration and prevents interstitial nephritis in MRL/lpr lupus-prone mice. iScience 27(11):111114 |
| abstractText | Systemic lupus erythematosus is a remitting relapsing autoimmune disease characterized by autoantibody production and multi-organ involvement. T cell epigenetic dysregulation plays an important role in the pathogenesis of lupus. We have previously demonstrated upregulation of the key epigenetic regulator EZH2 in CD4(+) T cells isolated from lupus patients. To further investigate the role of EZH2 in the pathogenesis of lupus, we generated a tamoxifen-inducible CD4(+) T cell Ezh2 conditional knockout mouse on the MRL/lpr lupus-prone background. We demonstrate that Ezh2 deletion abrogates lupus-like disease and prevents T cell differentiation. Single-cell analysis suggests impaired T cell function and activation of programmed cell death pathways in EZH2-deficient mice. Ezh2 deletion in CD4(+) T cells restricts TCR clonal repertoire and prevents kidney-infiltrating effector CD4(+) T cell expansion and tubulointerstitial nephritis, which has been linked to end-stage renal disease in patients with lupus nephritis. |
