Abstract
Memory programming of cytotoxic T cells (CTLs) by inflammatory cytokines can be regulated by mammalian target of rapamycin (mTOR). We have shown that inhibition of mTOR during CTL activation leads to the enhancement of memory, but the molecular mechanisms remain largely unknown. Using high-throughput RNA-Seq, we identified genes and functions in mouse CTLs affected by mTOR inhibition through rapamycin. Of the 43,221 identified transcripts, 184 transcripts were differentially expressed after rapamycin treatment, corresponding to 128 annotated genes. Of these genes, 114 were downregulated and only 14 were upregulated. Most importantly, 50 of them are directly related to cell death and survival. In addition, several genes such as CD62L are related to migration. Furthermore, we predicted downregulation of transcriptional regulators based on the total differentially expressed genes, as well as the subset of apoptosis-related genes. Quantitative PCR confirmed the differential expressions detected in RNA-Seq. We conclude that the regulatory function of rapamycin may work through inhibition of multiple genes related to apoptosis and migration, which enhance CTL survival into memory.
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Acknowledgments
We thank Mr. Ken Class for technical assistance. This work was partially supported by the National Institutes of Health GrantsR21AI095715A (to X. Z.) and Startup from UMD (to X. Z.). This work was supported in part by AFRI grant No. 2011-67015-30183 from USDA NIFA (to GEL). Mention of trade names or commercial products in this article is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the US Department of Agriculture. The USDA is an equal opportunity provider and employer.
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Elliot Mattson and Lingyang Xu are co-first authors.
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Mattson, E., Xu, L., Li, L. et al. Transcriptome profiling of CTLs regulated by rapamycin using RNA-Seq. Immunogenetics 66, 625–633 (2014). https://doi.org/10.1007/s00251-014-0790-5
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DOI: https://doi.org/10.1007/s00251-014-0790-5