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

来源：

IMMUNITY | 2021年 / 54卷 / 04期

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

页码：702 / +

页数：36

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