| First Author | Xing S | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 4 | Pages | 847-866 |
| PubMed ID | 30837262 | Mgi Jnum | J:275219 |
| Mgi Id | MGI:6305942 | Doi | 10.1084/jem.20182010 |
| Citation | Xing S, et al. (2019) Tcf1 and Lef1 are required for the immunosuppressive function of regulatory T cells. J Exp Med 216(4):847-866 |
| abstractText | Tcf1 and Lef1 have versatile functions in regulating T cell development and differentiation, but intrinsic requirements for these factors in regulatory T (T reg) cells remain to be unequivocally defined. Specific ablation of Tcf1 and Lef1 in T reg cells resulted in spontaneous multi-organ autoimmunity that became more evident with age. Tcf1/Lef1-deficient T regs showed reduced protection against experimentally induced colitis, indicative of diminished immuno-suppressive capacity. Transcriptomic analysis revealed that Tcf1 and Lef1 were responsible for positive regulation of a subset of T reg-overrepresented signature genes such as Ikzf4 and Izumo1r Unexpectedly, Tcf1 and Lef1 were necessary for restraining expression of cytotoxic CD8(+) effector T cell-associated genes in T reg cells, including Prdm1 and Ifng Tcf1 ChIP-seq revealed substantial overlap between Tcf1 and Foxp3 binding peaks in the T reg cell genome, with Tcf1-Foxp3 cooccupancy observed at key T reg signature and cytotoxic effector genes. Our data collectively indicate that Tcf1 and Lef1 are critical for sustaining T reg suppressive functions and preventing loss of self-tolerance. |
