| First Author | Yang L | Year | 2021 |
| Journal | Front Immunol | Volume | 12 |
| Pages | 722273 | PubMed ID | 34526995 |
| Mgi Jnum | J:311823 | Mgi Id | MGI:6762249 |
| Doi | 10.3389/fimmu.2021.722273 | Citation | Yang L, et al. (2021) Ddb1 Is Essential for the Expansion of CD4(+) Helper T Cells by Regulating Cell Cycle Progression and Cell Death. Front Immunol 12:722273 |
| abstractText | Follicular helper T (TFH) cells are specialized CD4(+) helper T cells that provide help to B cells in humoral immunity. However, the molecular mechanism underlying generation of TFH cells is incompletely understood. Here, we reported that Damage-specific DNA binding protein 1 (Ddb1) was required for expansion of CD4(+) helper T cells including TFH and Th1 cells, germinal center response, and antibody response to acute viral infection. Ddb1 deficiency in activated CD4(+) T cells resulted in cell cycle arrest at G2-M phase and increased cell death, due to accumulation of DNA damage and hyperactivation of ATM/ATR-Chk1 signaling. Moreover, mice with deletion of both Cul4a and Cul4b in activated CD4(+) T cells phenocopied Ddb1-deficient mice, suggesting that E3 ligase-dependent function of Ddb1 was crucial for genome maintenance and helper T-cell generation. Therefore, our results indicate that Ddb1 is an essential positive regulator in the expansion of CD4(+) helper T cells. |
