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IL-15 signaling promotes adoptive effector T-cell survival and memory formation in irradiation-induced lymphopenia

Overview of attention for article published in Cell & Bioscience, May 2016
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Title
IL-15 signaling promotes adoptive effector T-cell survival and memory formation in irradiation-induced lymphopenia
Published in
Cell & Bioscience, May 2016
DOI 10.1186/s13578-016-0098-2
Pubmed ID
Authors

Aizhang Xu, Kalpana Kalyanasundaram Bhanumathy, Jie Wu, Zhenmin Ye, Andrew Freywald, Scot C. Leary, Rongxiu Li, Jim Xiang

Abstract

Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8(+) effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression, respectively. Consistent with these findings, the expression of IL-7Rα and IL-15Rβ is down- and up-regulated, respectively, in vivo on transferred T-cells in an early phase post T-cell transfer in lymphopenia. We further show that in vitro IL-15 restimulation-induced memory T-cells (compared to IL-2 restimulation-induced effector T-cells) and in vivo transferred T-cells in irradiated IL-15-sufficient C57BL/6 mice (compared to IL-15-deficient IL-15 KO mice) have increased mitochondrial content, but less NADH and lower mitochondrial potential (ΔΨm), and demonstrate greater phosphorylation of signal transducers and activators of transcription-5 (STAT5) and Unc-51-like kinase-1 (ULK1), and higher expression of B-cell leukemia/lymphoma-2 (Bcl2) and memory-, autophagy- and mitochondrial biogenesis-related molecules. Irradiation-induced lymphopenia promotes effector T-cell survival via IL-15 signaling the STAT5/Bcl2 pathway, enhances T-cell memory formation via IL-15 activation of the forkhead-box family of transcription factor (FOXO)/eomesodermin (Eomes) memory and ULK1/autophagy-related gene-7 (ATG7) autophagy pathways, and via IL-15 activation of the mitochondrial remodeling. Our data thus identify some important targets to consider when designing potent adoptive T-cell immunotherapies of cancer.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 39 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 39 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 33%
Researcher 7 18%
Student > Master 4 10%
Student > Bachelor 3 8%
Professor > Associate Professor 2 5%
Other 2 5%
Unknown 8 21%
Readers by discipline Count As %
Immunology and Microbiology 8 21%
Biochemistry, Genetics and Molecular Biology 5 13%
Agricultural and Biological Sciences 5 13%
Medicine and Dentistry 5 13%
Engineering 3 8%
Other 4 10%
Unknown 9 23%

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 10 May 2016.
All research outputs
#6,644,202
of 7,679,268 outputs
Outputs from Cell & Bioscience
#150
of 175 outputs
Outputs of similar age
#223,664
of 267,539 outputs
Outputs of similar age from Cell & Bioscience
#17
of 17 outputs
Altmetric has tracked 7,679,268 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 175 research outputs from this source. They receive a mean Attention Score of 2.1. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 17 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.