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Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF.
Immunity ( IF 25.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.immuni.2019.12.002 Michael Delacher 1 , Charles D Imbusch 2 , Agnes Hotz-Wagenblatt 3 , Jan-Philipp Mallm 4 , Katharina Bauer 4 , Malte Simon 2 , Dania Riegel 5 , André F Rendeiro 6 , Sebastian Bittner 7 , Lieke Sanderink 7 , Asmita Pant 7 , Lisa Schmidleithner 7 , Kathrin L Braband 8 , Bernd Echtenachter 7 , Alexander Fischer 9 , Valentina Giunchiglia 2 , Petra Hoffmann 10 , Matthias Edinger 10 , Christoph Bock 11 , Michael Rehli 10 , Benedikt Brors 12 , Christian Schmidl 5 , Markus Feuerer 1
Immunity ( IF 25.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.immuni.2019.12.002 Michael Delacher 1 , Charles D Imbusch 2 , Agnes Hotz-Wagenblatt 3 , Jan-Philipp Mallm 4 , Katharina Bauer 4 , Malte Simon 2 , Dania Riegel 5 , André F Rendeiro 6 , Sebastian Bittner 7 , Lieke Sanderink 7 , Asmita Pant 7 , Lisa Schmidleithner 7 , Kathrin L Braband 8 , Bernd Echtenachter 7 , Alexander Fischer 9 , Valentina Giunchiglia 2 , Petra Hoffmann 10 , Matthias Edinger 10 , Christoph Bock 11 , Michael Rehli 10 , Benedikt Brors 12 , Christian Schmidl 5 , Markus Feuerer 1
Affiliation
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Specialized regulatory T (Treg) cells accumulate and perform homeostatic and regenerative functions in nonlymphoid tissues. Whether common precursors for nonlymphoid-tissue Treg cells exist and how they differentiate remain elusive. Using transcription factor nuclear factor, interleukin 3 regulated (Nfil3) reporter mice and single-cell RNA-sequencing (scRNA-seq), we identified two precursor stages of interleukin 33 (IL-33) receptor ST2-expressing nonlymphoid tissue Treg cells, which resided in the spleen and lymph nodes. Global chromatin profiling of nonlymphoid tissue Treg cells and the two precursor stages revealed a stepwise acquisition of chromatin accessibility and reprogramming toward the nonlymphoid-tissue Treg cell phenotype. Mechanistically, we identified and validated the transcription factor Batf as the driver of the molecular tissue program in the precursors. Understanding this tissue development program will help to harness regenerative properties of tissue Treg cells for therapy.
中文翻译：
非淋巴组织Treg细胞的前体存在于次级淋巴器官中，并由转录因子BATF编程。
专门的调节性T（Treg）细胞在非淋巴组织中积聚并执行稳态和再生功能。非淋巴组织Treg细胞的常见前体是否存在以及它们如何分化仍然不清楚。使用转录因子核因子，白介素3调节（Nfil3）记者小鼠和单细胞RNA测序（scRNA-seq），我们确定了表达白介素33（IL-33）受体ST2的非淋巴组织Treg细胞的两个前体阶段，驻留在脾和淋巴结中。非淋巴组织Treg细胞和两个前体阶段的整体染色质分析揭示了染色质可及性的逐步获取，并朝着非淋巴组织Treg细胞表型重编程。机械上，我们鉴定并验证了转录因子Batf作为前体分子组织程序的驱动力。了解该组织发育程序将有助于利用组织Treg细胞的再生特性进行治疗。
更新日期：2020-01-07
中文翻译：
非淋巴组织Treg细胞的前体存在于次级淋巴器官中，并由转录因子BATF编程。
专门的调节性T（Treg）细胞在非淋巴组织中积聚并执行稳态和再生功能。非淋巴组织Treg细胞的常见前体是否存在以及它们如何分化仍然不清楚。使用转录因子核因子，白介素3调节（Nfil3）记者小鼠和单细胞RNA测序（scRNA-seq），我们确定了表达白介素33（IL-33）受体ST2的非淋巴组织Treg细胞的两个前体阶段，驻留在脾和淋巴结中。非淋巴组织Treg细胞和两个前体阶段的整体染色质分析揭示了染色质可及性的逐步获取，并朝着非淋巴组织Treg细胞表型重编程。机械上，我们鉴定并验证了转录因子Batf作为前体分子组织程序的驱动力。了解该组织发育程序将有助于利用组织Treg细胞的再生特性进行治疗。
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