Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF

被引：138

作者：

Delacher, Michael ^{[1
,2
,3
]}

Imbusch, Charles D. ^{[4
,5
]}

Hotz-Wagenblatt, Agnes ^{[6
]}

Mallm, Jan-Philipp ^{[7
,8
]}

Bauer, Katharina ^{[7
,8
]}

Simon, Malte ^{[4
,5
]}

Riegel, Dania ^{[1
]}

Rendeiro, Andre F. ^{[9
]}

Bittner, Sebastian ^{[1
,2
]}

Sanderink, Lieke ^{[1
,2
]}

Pant, Asmita ^{[1
,2
]}

Schmidleithner, Lisa ^{[1
,2
]}

Braband, Kathrin L. ^{[3
]}

Echtenachter, Bernd ^{[1
,2
]}

Fischer, Alexander ^{[10
]}

Giunchiglia, Valentina ^{[4
,5
]}

Hoffmann, Petra ^{[1
,10
]}

Edinger, Matthias ^{[1
,10
]}

Bock, Christoph ^{[11
,12
,13
]}

Rehli, Michael ^{[1
,10
]}

Brors, Benedikt ^{[5
,14
,15
]}

Schmidl, Christian ^{[1
]}

Feuerer, Markus ^{[1
,2
,3
]}

机构：

[1] Regensburg Ctr Intervent Immunol RCI, Franz Josef Str Allee 11, D-93053 Regensburg, Germany

[2] Regensburg Univ, Chair Immunol, Franz Josef Str Allee 11, D-93053 Regensburg, Germany

[3] German Canc Res Ctr, Tumor Immunol Program, Immune Tolerance Grp, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[4] Heidelberg Univ, Fac Biosci, Neuenheimer Feld 234, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, Div Appl Bioinformat, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[6] German Canc Res Ctr, Genom & Prote Core Facil, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[7] German Canc Res Ctr, Div Chromatin Networks, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[8] German Canc Res Ctr, Single Cell Open Lab, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[9] Austrian Acad Sci, CeMM Res Ctr Mol Med, Lazarettgasse 14, A-1090 Vienna, Austria

[10] Univ Hosp Regensburg, Hematol & Oncol, Dept Internal Med 3, Franz Josef Str Allee 11, D-93053 Regensburg, Germany

[11] Med Univ Vienna, Dept Lab Med, Spitalgasse 23, A-1090 Vienna, Austria

[12] Max Planck Inst Informat, Saarland Informat Campus, D-66123 Saarbrucken, Germany

[13] Ludwig Boltzmann Inst Rare & Undiagnosed Dis, Lazarettgasse 14, A-1090 Vienna, Austria

[14] Natl Ctr Tumor Dis NCT, Neuenheimer Feld 460, D-69120 Heidelberg, Germany

[15] German Canc Res Ctr, German Canc Consortium DKTK, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

来源：

IMMUNITY | 2020年 / 52卷 / 02期

基金：

欧洲研究理事会;

关键词：

REGULATORY T-CELLS; DIFFERENTIATION; ACCUMULATION; AUTOIMMUNITY; POPULATION; ALIGNMENT; ELEMENTS; FATE;

D O I：

10.1016/j.immuni.2019.12.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：295 / +

页数：29

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