Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells

被引:90
作者
Delacher, Michael [1 ,2 ,3 ,4 ]
Simon, Malte [5 ,6 ]
Sanderink, Lieke [1 ,2 ]
Hotz-Wagenblatt, Agnes [7 ]
Wuttke, Marina [1 ,2 ]
Schambeck, Kathrin [1 ,2 ]
Schmidleithner, Lisa [1 ,2 ]
Bittner, Sebastian [1 ,2 ]
Pant, Asmita [1 ,2 ]
Ritter, Uwe [1 ,2 ]
Hehlgans, Thomas [1 ,2 ]
Riegel, Dania [1 ]
Schneider, Verena [8 ,9 ]
Groeber-Becker, Florian Kai [8 ,9 ]
Eigenberger, Andreas [10 ]
Gebhard, Claudia [1 ]
Strieder, Nicholas [1 ]
Fischer, Alexander [1 ,11 ]
Rehli, Michael [1 ,11 ]
Hoffmann, Petra [1 ,11 ]
Edinger, Matthias [1 ,11 ]
Strowig, Till [12 ,14 ,15 ]
Huehn, Jochen [13 ,15 ]
Schmidl, Christian [1 ]
Werner, Jens M. [16 ]
Prantl, Lukas [10 ]
Brors, Benedikt [6 ,17 ,18 ]
Imbusch, Charles D. [6 ]
Feuerer, Markus [1 ,2 ]
机构
[1] Regensburg Ctr Intervent Immunol RCI, Regensburg, Germany
[2] Univ Regensburg, Chair Immunol, D-93053 Regensburg, Germany
[3] Univ Med Ctr Mainz, Inst Immunol, D-55131 Mainz, Germany
[4] Univ Med Ctr Mainz, Res Ctr Immunotherapy, D-55131 Mainz, Germany
[5] Heidelberg Univ, Fac Biosci, D-69120 Heidelberg, Germany
[6] German Canc Res Ctr, Div Appl Bioinformat, D-69120 Heidelberg, Germany
[7] German Canc Res Ctr, Core Facil Omics IT & Data Management ODCF, D-69120 Heidelberg, Germany
[8] Univ Hosp Wurzburg, Dept Tissue Engn & Regenerat Med TERM, D-97070 Wurzburg, Germany
[9] Translat Ctr Regenerat Therapies TLZ RT, Fraunhofer Inst Silicate Res ISC, D-97082 Wurzburg, Germany
[10] Univ Hosp Regensburg, Dept Plast Hand & Reconstruct Surg, D-93053 Regensburg, Germany
[11] Univ Hosp Regensburg, Dept Internal Med 3, D-93053 Regensburg, Germany
[12] Helmholtz Ctr Infect Res, Dept Microbial Immune Regulat, D-38124 Braunschweig, Germany
[13] Helmholtz Ctr Infect Res, Dept Expt Immunol, D-38124 Braunschweig, Germany
[14] Hannover Med Sch, D-30625 Hannover, Germany
[15] Hannover Med Sch, Cluster Excellence 2155, RESIST, D-30625 Hannover, Germany
[16] Univ Hosp Regensburg, Dept Surg, D-93053 Regensburg, Germany
[17] Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany
[18] German Canc Res Ctr, German Canc Consortium DKTK, D-69120 Heidelberg, Germany
基金
欧洲研究理事会;
关键词
GENOME BROWSER; POPULATION; ALIGNMENT; LINEAGE; BATF;
D O I
10.1016/j.immuni.2021.03.007
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Murine regulatory T (Treg) cells in tissues promote tissue homeostasis and regeneration. We sought to identify features that characterize human Treg cells with these functions in healthy tissues. Single-cell chromatin accessibility profiles of murine and human tissue Treg cells defined a conserved, microbiota-independent tissue-repair Treg signature with a prevailing footprint of the transcription factor BATF. This signature, combined with gene expression profiling and TCR fate mapping, identified a population of tissue-like Treg cells in human peripheral blood that expressed BATF, chemokine receptor CCR8 and HLA-DR. Human BATF(+) CCR8(+) Treg cells from normal skin and adipose tissue shared features with nonlymphoid T follicular helper-like (Tfh-like) cells, and induction of a Tfh-like differentiation program in naive human Treg cells partially recapitulated tissue Treg regenerative characteristics, including wound healing potential. Human BATF(+) CCR8(+) Treg cells from healthy tissue share features with tumor-resident Treg cells, highlighting the importance of understanding the context-specific functions of these cells.
引用
收藏
页码:702 / +
页数:36
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