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Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, March 2015
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Title
Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A
Published in
Proceedings of the National Academy of Sciences of the United States of America, March 2015
DOI 10.1073/pnas.1418316112
Pubmed ID
Authors

Lauren P Schewitz-Bowers, Philippa J P Lait, David A Copland, Ping Chen, Wenting Wu, Ashwin D Dhanda, Barbara P Vistica, Emily L Williams, Baoying Liu, Shayma Jawad, Zhiyu Li, William Tucker, Sima Hirani, Yoshiyuki Wakabayashi, Jun Zhu, Nida Sen, Becky L Conway-Campbell, Igal Gery, Andrew D Dick, Lai Wei, Robert B Nussenblatt, Richard W J Lee

Abstract

Glucocorticoids remain the cornerstone of treatment for inflammatory conditions, but their utility is limited by a plethora of side effects. One of the key goals of immunotherapy across medical disciplines is to minimize patients' glucocorticoid use. Increasing evidence suggests that variations in the adaptive immune response play a critical role in defining the dose of glucocorticoids required to control an individual's disease, and Th17 cells are strong candidate drivers for nonresponsiveness [also called steroid resistance (SR)]. Here we use gene-expression profiling to further characterize the SR phenotype in T cells and show that Th17 cells generated from both SR and steroid-sensitive individuals exhibit restricted genome-wide responses to glucocorticoids in vitro, and that this is independent of glucocorticoid receptor translocation or isoform expression. In addition, we demonstrate, both in transgenic murine T cells in vitro and in an in vivo murine model of autoimmunity, that Th17 cells are reciprocally sensitive to suppression with the calcineurin inhibitor, cyclosporine A. This result was replicated in human Th17 cells in vitro, which were found to have a conversely large genome-wide shift in response to cyclosporine A. These observations suggest that the clinical efficacy of cyclosporine A in the treatment of SR diseases may be because of its selective attenuation of Th17 cells, and also that novel therapeutics, which target either Th17 cells themselves or the effector memory T-helper cell population from which they are derived, would be strong candidates for drug development in the context of SR inflammation.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 13 28%
Student > Ph. D. Student 10 21%
Student > Doctoral Student 4 9%
Student > Master 4 9%
Other 3 6%
Other 5 11%
Unknown 8 17%
Readers by discipline Count As %
Medicine and Dentistry 11 23%
Agricultural and Biological Sciences 7 15%
Immunology and Microbiology 7 15%
Biochemistry, Genetics and Molecular Biology 4 9%
Computer Science 2 4%
Other 6 13%
Unknown 10 21%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. 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 28 June 2021.
All research outputs
#8,219,054
of 24,625,114 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#64,491
of 101,438 outputs
Outputs of similar age
#92,606
of 266,965 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#727
of 1,012 outputs
Altmetric has tracked 24,625,114 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one is in the 15th percentile – i.e., 15% 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 266,965 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
We're also able to compare this research output to 1,012 others from the same source and published within six weeks on either side of this one. This one is in the 26th percentile – i.e., 26% of its contemporaries scored the same or lower than it.