Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape
Interleukin 2 modulates thymic-derived regulatory T cell epigenetic landscape
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DOI：
10.1038/s41467-018-07806-6
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发表时间：
2018-12-18
影响因子：
16.6
通讯作者：
Lauvau, Gregoire
中科院分区：
文献类型：
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作者：
Chorro, Laurent;Suzuki, Masako;Lauvau, Gregoire
Foxp 3（+）CD 4（+）调节性T（T-reg）细胞对于预防致命性自身免疫和维护体内免疫稳态至关重要。虽然转录因子Foxp 3和IL-2信号的表达都是Treg细胞的发育和功能所需的，但在T细胞受体（TCR）触发后的胸腺选择期间发生向Treg细胞谱系的定型，并且在Foxp 3的表达之前。TCR以外的信号是否有助于建立T-reg细胞表观遗传和功能同一性仍然是未知的。在这里，我们使用IL-2信号转导减少的小鼠模型，表明IL-2调节CD 4（+）胸腺细胞中先锋因子SATB 1的定位，并控制胸腺源性Treg细胞的全基因组染色质可及性。我们还表明，Treg细胞只接受低IL-2信号可以抑制内源性，但不是WT自身反应性T细胞反应在体外和体内。我们的研究结果对体内重编程Treg细胞的潜在治疗策略具有广泛的意义。
Foxp3(+)CD4(+) regulatory T (T-reg) cells are essential for preventing fatal autoimmunity and safeguard immune homeostasis in vivo. While expression of the transcription factor Foxp3 and IL-2 signals are both required for the development and function of Treg cells, the commitment to the Treg cell lineage occurs during thymic selection upon T cell receptor (TCR) triggering, and precedes the expression of Foxp3. Whether signals beside TCR contribute to establish T-reg cell epigenetic and functional identity is still unknown. Here, using a mouse model with reduced IL-2 signaling, we show that IL-2 regulates the positioning of the pioneer factor SATB1 in CD4(+) thymocytes and controls genome wide chromatin accessibility of thymic-derived Treg cells. We also show that Treg cells receiving only low IL-2 signals can suppress endogenous but not WT autoreactive T cell responses in vitro and in vivo. Our findings have broad implications for potential therapeutic strategies to reprogram Treg cells in vivo.