研究揭示非淋巴組織調節性T細胞前體的產生機制
作者：
小柯機器人發布時間：2020/1/8 11:13:02
近日，德國雷根斯堡大學Markus Feuerer及其研究組發現，非淋巴組織調節性T（Treg）細胞的前體存在於次級淋巴器官中，並由轉錄因子BATF調控。該研究2020年1月7日在線發表於國際學術期刊《免疫》。
使用轉錄因子核因子、白介素3調節（Nfil3）的報告小鼠和單細胞RNA測序（scRNA-seq），研究人員確定了表達白介素33（IL-33）受體ST2的非淋巴組織Treg細胞的兩個前體階段，其駐留在脾和淋巴結中。非淋巴組織Treg細胞和兩個前體階段的整體染色質分析揭示了染色質可及性的逐步獲取，並朝著非淋巴組織Treg細胞表型重編程。從機制上講，研究人員確定並驗證了轉錄因子Batf作為前體細胞分子組織程序的驅動因子。了解該組織發育程序將有助於利用組織Treg細胞的再生特性進行治療。
據介紹，專門的reg細胞在非淋巴組織中積聚並執行體內平衡和再生功能。是否存在非淋巴組織Treg細胞的共同前體以及它們如何分化仍然不清楚。
附：英文原文
Title: Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF
Author: Michael Delacher, Charles D. Imbusch, Agnes Hotz-Wagenblatt, Jan-Philipp Mallm, Katharina Bauer, Malte Simon, Dania Riegel, André F. Rendeiro, Sebastian Bittner, Lieke Sanderink, Asmita Pant, Lisa Schmidleithner, Kathrin L. Braband, Bernd Echtenachter, Alexander Fischer, Valentina Giunchiglia, Petra Hoffmann, Matthias Edinger, Christoph Bock, Michael Rehli, Benedikt Brors, Christian Schmidl, Markus Feuerer
Issue&Volume: January 7, 2020
Abstract: 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.
DOI: 10.1016/j.immuni.2019.12.002
Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30498-4