| First Author | Mookerjee-Basu J | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 5 | Pages | e48904 |
| PubMed ID | 32212315 | Mgi Jnum | J:306473 |
| Mgi Id | MGI:6448830 | Doi | 10.15252/embr.201948904 |
| Citation | Mookerjee-Basu J, et al. (2020) Suppression of Ca(2+) signals by EGR4 controls Th1 differentiation and anti-cancer immunity in vivo. EMBO Rep 21(5):e48904 |
| abstractText | While the zinc finger transcription factors EGR1, EGR2, and EGR3 are recognized as critical for T-cell function, the role of EGR4 remains unstudied. Here, we show that EGR4 is rapidly upregulated upon TCR engagement, serving as a critical "brake" on T-cell activation. Hence, TCR engagement of EGR4(-/-) T cells leads to enhanced Ca(2+) responses, driving sustained NFAT activation and hyperproliferation. This causes profound increases in IFNgamma production under resting and diverse polarizing conditions that could be reversed by pharmacological attenuation of Ca(2+) entry. Finally, an in vivo melanoma lung colonization assay reveals enhanced anti-tumor immunity in EGR4(-/-) mice, attributable to Th1 bias, Treg loss, and increased CTL generation in the tumor microenvironment. Overall, these observations reveal for the first time that EGR4 is a key regulator of T-cell differentiation and function. |
