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| Status |
Public on May 14, 2018 |
| Title |
TIGIT+ iTregs elicited by human regulatory macrophages control T cell immunity |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based, adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4+ T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4+ T cells to IL-10-producing, TIGIT+ FoxP3+ induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs (miTregs) relies on multiple, non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-β, retinoic acid, Notch and progestagen-associated endometrial protein. Preoperative administration of donor-derived Mregs to living-donor kidney transplant recipients results in an acute increase in circulating TIGIT+ Tregs. These results suggest a feed-forward mechanism by which Mreg treatment promotes allograft acceptance through rapid induction of direct pathway Tregs.
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| Overall design |
To better characterise the phenotype of human miTregs, whole genome gene expression profiling studies by microarray were performed. Mregs and IFN-γ Mφ were generated from CD14+ monocytes of 5 healthy donors. Seven days later, CD3+ T cells were isolated from 5 unrelated healthy donors and split into two lots: From the first lot, a pure population of fresh CD4+ T cells was obtained by flow-sorting and total RNA was extracted; the second lot of T cells was added into direct co-culture with allogeneic Mregs or IFN-γ Mφ at a 1:1 ratio for 5 days, or were cultured alone without stimulation for 5 days. After coculture, CD4+ and CD8+ T cells were flow-sorted and total RNA was extracted. Microarray analysis was performed on the Agilent Whole Human Genome Oligo Microarray 8x60K platform. Hence, a dataset was generated comprising eight sample groups (S1-S8) representing four CD4+ T cell populations and four CD8+ T cell populations from 5 independent donors produced by single-colour hybridisations.
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| Contributor(s) |
Riquelme P, Tomiuk S, Hutchinson JA |
| Citation(s) |
30030423 |
| Submission date |
Jul 30, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
James Alexander Hutchinson |
| E-mail(s) |
james.hutchinson@klinik.uni-regensburg.de
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| Organization name |
University Hospital Regensburg
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| Department |
General Surgery
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| Lab |
Transplant Immunology
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| Street address |
Franz-Josef-Strauss-Allee-11
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| City |
Regensburg |
| State/province |
Bavaria |
| ZIP/Postal code |
93053 |
| Country |
Germany |
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| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA213736 |
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