T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Medical Faculty Heidelberg, Heidelberg University, Germany.
FEBS Lett. 2019 May;593(10):1020-1029. doi: 10.1002/1873-3468.13393. Epub 2019 May 6.
To maintain immune tolerance, effector T-cell (Teff) responses must be checked by the regulatory T cells (Tregs) in time. It remains incompletely understood how Tregs sense real-time Teff activation. Here, we report that the AP-1 transcription factor JunB, which is induced in Teffs upon T-cell receptor (TCR) activation, is also increased in Tregs by TCR stimuli. Treg-specific deletion of Junb impairs Treg identity, causes uncontrolled inflammatory cytokine production by Teffs and leads to the T-box transcription factor T-bet-dependent spontaneous inflammation. Furthermore, JunB deficiency in Tregs unleashes antitumor Teff responses in a mouse model of melanoma. We conclude that JunB alarms Tregs of the emerging Teff activation and synchronizes immune regulation with the immune reaction in autoimmunity and cancer.
为了维持免疫耐受，效应 T 细胞（Teff）的反应必须及时被调节性 T 细胞（Tregs）所抑制。Tregs 如何实时感知 Teff 激活仍不完全清楚。在这里，我们报告称，AP-1 转录因子 JunB 在 TCR 激活后 Teffs 中诱导，也被 TCR 刺激在 Tregs 中增加。Treg 特异性 Junb 缺失会损害 Treg 的特性，导致 Teffs 产生不受控制的炎性细胞因子，并导致 T 框转录因子 T-bet 依赖性自发性炎症。此外，Treg 中的 JunB 缺陷会在黑色素瘤的小鼠模型中引发抗肿瘤 Teff 反应。我们得出结论，JunB 会向 Tregs 发出 Teff 激活的警报，并使免疫调节与自身免疫和癌症中的免疫反应同步。
