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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 03, 2014 |
| Title |
Modification of T cell responses by stem cell mobilization requires direct signalling of the T cell by G-CSF and IL-10 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The majority of allogeneic stem cell transplants are currently undertaken using G-CSF mobilized peripheral blood stem cells. G-CSF has diverse biological effects on a broad range of cells and IL-10 is a key regulator of many of these effects. Using mixed radiation chimeras in which the haematopoietic or non-haematopoietic compartments were wild-type (WT), IL-10–/–, G-CSFR–/– or combinations thereof we demonstrated that the attenuation of alloreactive T cell responses after with G-CSF mobilization required direct signalling of the T cell by both G-CSF and IL-10. IL-10 was generated principally by radio-resistant tissue, and was not required to be produced by T cells. G-CSF mobilization significantly modulated the transcription profile of CD4+CD25+ regulatory T cells, promoted their expansion in the donor and recipient and their depletion significantly increased graft-versus-host disease (GVHD). In contrast, stem cell mobilization with the CXCR4 antagonist AMD3100 did not alter the donor T cell’s ability to induce acute GVHD. These studies provide an explanation for the effects of G-CSF on T cell function and demonstrate that IL-10 is required to license regulatory function but T cell production of IL-10 is not itself required for the attenuation GVHD. Although administration of CXCR4 antagonists is an efficient means of stem cell mobilization, this fails to evoke the immunomodulatory effects seen during G-CSF mobilization. These data provide a compelling rationale for considering the immunological benefits of G-CSF in selecting mobilization protocols for allogeneic stem cell transplantation.
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| Overall design |
Single colour, Illumina MouseRef-8 v2.0 Beadarrays.
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| Contributor(s) |
MacDonald KP, Le Texier L, Zhang P, Morris H, Kuns RD, Lineburg KE, Leveque L, Don AL, Markey KA, Vuckovic S, Otzen Bagger F, Boyle G, Blazar BR, Hill GR |
| Citation(s) |
24585878 |
| Submission date |
Feb 02, 2014 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Glen M Boyle |
| E-mail(s) |
Glen.Boyle@qimr.edu.au
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| Phone |
+61 7 3362 0319
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| Organization name |
QIMR Berghofer Medical Research Insitute
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| Department |
Department of Cell and Molecular Biology, Cancer Program
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| Lab |
Cancer Drug Mechanisms Group
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| Street address |
300 Herston Road Herston
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| City |
Brisbane |
| State/province |
Queensland |
| ZIP/Postal code |
4006 |
| Country |
Australia |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA237186 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE54616_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE54616_non-normalized.txt.gz |
932.1 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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