Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells
- Trinity College Dublin, Ireland
- Brigham and Women's Hospital, United States
- University of Melbourne, Australia
Abstract
Innate T cells, including CD1d-restricted invariant natural killer T (iNKT) cells, are characterized by their rapid activation in response to non-peptide antigens, such as lipids. While the transcriptional profiles of naive, effector and memory adaptive T cells have been well studied, less is known about transcriptional regulation of different iNKT cell activation states. Here, using single cell RNA-sequencing, we performed longitudinal profiling of activated murine iNKT cells, generating a transcriptomic atlas of iNKT cell activation states. We found that transcriptional signatures of activation are highly conserved among heterogeneous iNKT cell populations, including NKT1, NKT2 and NKT17 subsets, and human iNKT cells. Strikingly, we found that regulatory iNKT cells, such as adipose iNKT cells, undergo blunted activation, and display constitutive enrichment of memory-like cMAF+ and KLRG1+ populations. Moreover, we identify a conserved cMAF-associated transcriptional network among NKT10 cells, providing novel insights into the biology of regulatory and antigen experienced iNKT cells.
Data availability
Sequencing data have been deposited in GEO under accession code GSE190201.
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Single cell analysis of activated iNKT cells from murine epididymal adipose tissue and spleenNCBI Gene Expression Omnibus, GSE190201.
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Single cell analysis of iNKT cells from murine epididymal adipose tissue and spleenNCBI Gene Expression Omnibus, GSE142845.
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Single-cell RNA-seq of human peripheral blood NKT cellsNCBI Gene Expression Omnibus, GSE128243.
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NKT-10 cells represent a novel invariant NKT cell subset with regulatory characteristicsNCBI Gene Expression Omnibus, GSE47959.
Article and author information
Author details
Funding
American Diabetes Association (1-16-JDF-061)
- Lydia Lynch
National Institutes of Health (R01AI134861)
- Lydia Lynch
European Research Council (679173)
- Lydia Lynch
Science Foundation Ireland
- Harry Kane
- Lydia Lynch
National Institutes of Health (AI113046)
- Michael P Brenner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal work was approved and conducted in compliance with the Trinity College Dublin University Ethics Committee and the Health Products Regulatory Authority Ireland, and the Institutional Animal Care and Use Committee guidelines of The Dana Farber Cancer Institute and Harvard Medical School.
Copyright
© 2022, Kane et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells
eLife 11:e76586.
https://doi.org/10.7554/eLife.76586
