Journal
GENETICS
Volume 201, Issue 3, Pages 1017-U419Publisher
GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.115.179176
Keywords
microRNA regulation; adaptive immunity; development
Categories
Funding
- National Institutes of Health (NIH) [2 U42 OD011158, 1S10OD010693, R01AI105265, R01AI110613]
- Cornell University
- Cornell Center for Vertebrate Genomics
- National Science Foundation [DGE-1144153]
- Empire State Stem Cell Fund
- New York State Department of Health (NYS-DOH) [C026718]
- [R01GM105668]
- [P50HD076210]
Ask authors/readers for more resources
Immunological memory, which protects organisms from re-infection, is a hallmark of the mammalian adaptive immune system and the underlying principle of vaccination. In early life, however, mice and other mammals are deficient at generating memory CD8+ T cells, which protect organisms from intracellular pathogens. The molecular basis that differentiates adult and neonatal CD8+ T cells is unknown. MicroRNAs (miRNAs) are both developmentally regulated and required for normal adult CD8+ T cell functions. We used next-generation sequencing to identify mouse miRNAs that are differentially regulated in adult and neonatal CD8+ T cells, which may contribute to the impaired development of neonatal memory cells. The miRNA profiles of adult and neonatal cells were surprisingly similar during infection; however, we observed large differences prior to infection. In particular, miR-29 and miR-130 have significant differential expression between adult and neonatal cells before infection. Importantly, using RNA-Seq, we detected reciprocal changes in expression of messenger RNA targets for both miR-29 and miR-130. Moreover, targets that we validated include Eomes and Tbx21, key genes that regulate the formation of memory CD8+ T cells. Notably, age-dependent changes in miR-29 and miR-130 are conserved in human CD8+ T cells, further suggesting that these developmental differences are biologically relevant. Together, these results demonstrate that miR-29 and miR-130 are likely important regulators of memory CD8+ T cell formation and suggest that neonatal cells are committed to a short-lived effector cell fate prior to infection.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available