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HIF-1α inhibitor echinomycin reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect

Overview of attention for article published in Journal of Translational Medicine, February 2017
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Title
HIF-1α inhibitor echinomycin reduces acute graft-versus-host disease and preserves graft-versus-leukemia effect
Published in
Journal of Translational Medicine, February 2017
DOI 10.1186/s12967-017-1132-9
Pubmed ID
Authors

Yushi Yao, Lei Wang, Jihao Zhou, Xinyou Zhang

Abstract

Acute graft-versus-host disease (aGVHD) remains a major obstacle against favorable clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T helper cells including Th17 play key roles in aGVHD pathogenesis. Donor regulatory T cell (Tregs) adoptive therapy reduces aGVHD without weakening graft-versus-leukemia effect (GVL) in both mouse and human, although the purification and ex vivo expansion of Tregs in clinical scenarios remain costly and technically demanding. Hypoxia-inducible factor 1 alpha (HIF-1α) is a key molecule switch that attenuates Treg but promotes Th17 development. However, whether pharmacological inhibition of HIF-1α reduces aGVHD via increasing Treg development and diminishing Th17 responses remains unexplored. By using alloantigen-specific mixed lymphocyte culture and murine models of aGVHD and GVL, we evaluated the impacts of HIF-1α inhibition by echinomycin on the alloantigen-specific CD4 T cell responses ex vivo, as well as on aGVHD and GVL effect following allo-HSCT. Ex vivo echinomycin treatment resulted in increased number of Tregs in the culture as well as reduced alloantigen-specific Th17 and Th1 responses. In vivo echinomycin treatment reduced GVHD scores and prolonged survival of mice following allo-HSCT, which is associated with increased number of donor Tregs and reduced number of Th17 and Th1 in lymphoid tissues. In murine model of leukemia, echinomycin treatment preserved GVL effect and prolonged leukemia free survival following allo-HSCT. Echinomycin treatment reduces aGVHD and preserves GVL effect via increasing donor Treg development and diminishing alloantigen-specific Th17 and Th1 responses following allo-HSCT, presumably via direct inhibition of HIF-1α that results in preferential Treg differentiation during alloantigen-specific CD4 T cell responses. These findings highlight pharmacological inhibition of HIF-1α as a promising strategy in GVHD prophylaxis.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 36%
Researcher 3 27%
Student > Postgraduate 1 9%
Student > Master 1 9%
Student > Doctoral Student 1 9%
Other 1 9%
Readers by discipline Count As %
Medicine and Dentistry 4 36%
Agricultural and Biological Sciences 2 18%
Biochemistry, Genetics and Molecular Biology 2 18%
Immunology and Microbiology 1 9%
Psychology 1 9%
Other 1 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 09 December 2018.
All research outputs
#10,401,476
of 13,044,924 outputs
Outputs from Journal of Translational Medicine
#2,224
of 2,592 outputs
Outputs of similar age
#242,374
of 344,995 outputs
Outputs of similar age from Journal of Translational Medicine
#2
of 3 outputs
Altmetric has tracked 13,044,924 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,592 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 344,995 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 17th percentile – i.e., 17% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.