Dataset Information

Cellular and transcriptional impacts of ruxolitinib versus IFN-gamma neutralization in mouse models of HLH

ABSTRACT: Cellular and transcriptional impacts of ruxolitinib versus IFN-gamma neutralization in mouse models of HLH

PROVIDER: PRJNA903960 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	SRR22366715_1.fastq.gz	Fastqsanger.gz
	SRR22366715_2.fastq.gz	Fastqsanger.gz
	SRR22366716_1.fastq.gz	Fastqsanger.gz
	SRR22366716_2.fastq.gz	Fastqsanger.gz
	SRR22366717_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 30

Similar Datasets

Project description:Hemophagocytic lymphohistiocytosis is a cytokine storm syndrome characterized by the excessive activation of myeloid and T cells. In primary HLH (pHLH), disease pathophysiology is driven by CD8 T cells proliferation and IFNg production. Therefore, targeting IFNg has been a viable option for the treatment of HLH. Since many cytokines that signaling throught the JAK/STAT pathway, including IFNg, largely drive cytokine storm in HLH, we and others have demonstrated that targeting JAK1/2 with ruxolitinib is effective in ameliorating disease manifestations in pre-clinical models of HLH. Both IFNg and ruxolitinib treatments have also shown great efficacy in dampening inflammation in patients with HLH, albeit not completely. Since ruxolitinib treatment does not fully inhibit IFNg production, we sought to determine the effect of combining ruxolitinib treatment with IFNg neutralization as a treatment option in a LCMV-infected Prf1 mice. We aimed to elucidate the effects of these treatments on the main hematologic and cellular parameters of disease. Moreover, we determined the main changes in the transcriptional landscape on CD8 T cells isolated from mice infected with LCMV either untreated or treated with aIFNg, ruxolitinib, or combination treatments. We demonstrate that combination treatment was very effective in reversing anemia and thrombocytopenia, but failed to reduce splenomegaly, hypercytokinemia, and myeloid and T cell numbers compared to ruxolitinib treatment. Transcriptional analysis revealed distinct pathways targeted by aIFNg and ruxolitinib; while aIFNg was more effective in downregulating the expression of interferon gamma response genes, allograft rejection, and complement genes, ruxolitinib treated CD8 T cells displayed a reduction in expression of genes involved in reactive oxygen species, glycolysis, E2F targets, and protein secretion pathways. Therefore, this study provide novel insights on the effects of combining ruxolitinib treatment with IFNg neutralization in the treatment of primary HLH.

Dataset Information

Cellular and transcriptional impacts of ruxolitinib versus IFN-gamma neutralization in mouse models of HLH

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets