Nociceptive nerves regulate haematopoietic stem cell mobilization
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA657999 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12475100_1.fastq.gz | Fastqsanger.gz | |||
| SRR12475100_2.fastq.gz | Fastqsanger.gz | |||
| SRR12475101_1.fastq.gz | Fastqsanger.gz | |||
| SRR12475101_2.fastq.gz | Fastqsanger.gz | |||
| SRR12475102_1.fastq.gz | Fastqsanger.gz |
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Project description: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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