Longitudinal analysis of invariant natural killer T cell activation reveals a cMAF-associated transcriptional state of NKT10 cells

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...

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Bibliographic Details
Published in:eLife 2022-12, Vol.11
Main Authors: Kane, Harry, LaMarche, Nelson M, Ní Scannail, Áine, Garza, Amanda E, Koay, Hui-Fern, Azad, Adiba I, Kunkemoeller, Britta, Stevens, Brenneth, Brenner, Michael B, Lynch, Lydia
Format: Article
Language:English
Subjects:
activation
adipose tissue
Analysis
Animals
Antigens
Approximation
Biology
Body fat
CD1d antigen
Cell activation
Cell cycle
cellular metabolism
Computational and Systems Biology
Gene expression
Gene Expression Regulation
Gene regulation
Genetic aspects
Genetic transcription
Genotype & phenotype
Histograms
Humans
Immunological memory
Immunology and Inflammation
iNKT cells
KLRG1 protein
Lipids
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Memory cells
Metabolism
Mice
Natural killer cells
Natural Killer T-Cells
scRNA-Seq
T cells
Transcription
Transcription activation
Transcription factors
transcriptional remodeling
Transcriptomics
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Summary: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 the 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.76586