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| Status |
Public on Jan 01, 2024 |
| Title |
Donor regulatory T cells rapidly adapt to recipient tissues to control acute graft-versus-host disease [bulk RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Adoptive transfer of donor regulatory T cells (Treg) is a promising treatment option for Graft-versus-Host disease (GvHD), but has not yet found its way into routine clinical practice. To map distinctive properties of protective Treg (generated by either polyclonal or allogeneic in vitro expansion), we followed their fate in recipient organs (spleen, liver, colon) in a prophylactic mouse model of MHC-mismatched bone-marrow transplantation (BMT). Using comprehensive gene expression and T cell receptor profiling, we show that both in vitro expansion protocols generated Treg products that preserved hallmark Treg properties, ameliorated GvHD symptoms, retained their phenotypic plasticity and rapidly acquired organ-specific gene expression profiles after BMT, comparable to their tissue-resident counterparts. When co-transplanted with GvHD-inducing T cells, Treg enabled hallmark suppressive and cytotoxic features, most evidently in the colon. Dominant Treg T cell receptor clonotypes were evenly distributed between organs and across recipients, suggesting a major role of ubiquitous alloantigen-specific Treg in controlling GvHD. Effective protection inversely correlated with the relative abundance of organ-specific Treg, that were transcriptionally distinct, less “activated” and preferentially accumulated in the colon of recipients receiving polyclonally expanded Treg. In summary, we provide a detailed atlas of Treg selection and adaptation in the prophylactic therapy of GvHD.
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| Overall design |
total RNA expression profiles of independent isolations of C57BL/6 Treg from spleen (fresh, d0, homeostatic state),liver and colon (homeostatic state), in vitro expanded Treg (allo, poly, d11-14), or re-isolated Treg (spleen, liver, colon) 7d post transplant in either BMT control or GvHD models
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| Contributor(s) |
Dittmar DJ, Rehli M |
| Citation missing |
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| Submission date |
Jan 26, 2023 |
| Last update date |
Jan 01, 2024 |
| Contact name |
Michael Rehli |
| E-mail(s) |
michael.rehli@klinik.uni-r.de
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| Organization name |
University Hospital Regensburg
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| Department |
Internal Med III
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| Street address |
F.-J.-Strauss-Allee 11
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| City |
Regensburg |
| ZIP/Postal code |
93042 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (105)
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| This SubSeries is part of SuperSeries: |
| GSE223800 |
Donor regulatory T cells rapidly adapt to recipient tissues to control acute graft-versus-host disease |
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| Relations |
| BioProject |
PRJNA928406 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE223796_RNAseq_bulk_RawReadCountMatrix.txt.gz |
3.7 Mb |
(ftp)(http) |
TXT |
| GSE223796_RNAseq_bulk_normalizedReadCountMatrix.txt.gz |
9.3 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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