Jayati Mookerjee-Basu, Robert Hooper, Scott Gross, Bryant Schultz, Christina K Go, Elsie Samakai, Jonathan Ladner, Emmanuelle Nicolas, Yuanyuan Tian, Bo Zhou, M Raza Zaidi, Warren Tourtellotte, Shan He, Yi Zhang, Dietmar J Kappes, Jonathan Soboloff
EMBO reports 2020 May 06While 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 Ca2+ responses, driving sustained NFAT activation and hyperproliferation. This causes profound increases in IFNγ production under resting and diverse polarizing conditions that could be reversed by pharmacological attenuation of Ca2+ 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. © 2020 The Authors.
Jayati Mookerjee-Basu, Robert Hooper, Scott Gross, Bryant Schultz, Christina K Go, Elsie Samakai, Jonathan Ladner, Emmanuelle Nicolas, Yuanyuan Tian, Bo Zhou, M Raza Zaidi, Warren Tourtellotte, Shan He, Yi Zhang, Dietmar J Kappes, Jonathan Soboloff. Suppression of Ca2+ signals by EGR4 controls Th1 differentiation and anti-cancer immunity in vivo. EMBO reports. 2020 May 06;21(5):e48904
PMID: 32212315
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