Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF
Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF
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DOI：
10.1016/j.immuni.2019.12.002
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发表时间：
2020-02-18
期刊：
影响因子：
32.4
通讯作者：
Feuerer, Markus
中科院分区：
文献类型：
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作者：
Delacher, Michael;Imbusch, Charles D.;Feuerer, Markus
特化调节性T细胞（Treg）在非淋巴组织中积累并执行稳态和再生功能。非淋巴组织Treg细胞的共同前体是否存在以及它们如何分化仍然是一个谜。利用转录因子核因子、白细胞介素3调节（Nfil3）报告小鼠和单细胞rna测序（scRNA-seq），我们鉴定了两个表达白细胞介素33 （IL-33）受体st2的非淋巴组织Treg细胞的前体阶段，它们位于脾脏和淋巴结。非淋巴组织Treg细胞的整体染色质谱和两个前体阶段揭示了染色质可及性的逐步获得和向非淋巴组织Treg细胞表型的重编程。在机制上，我们确定并验证了转录因子Batf作为前体分子组织程序的驱动程序。了解这个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。
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 non lymphoid 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.