Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage.
Nyambayar DashtsoodolTomokuni ShigeuraMinako AiharaRitsuko OzawaSatoshi KojoMichishige HaradaTakaho A EndoTakashi WatanabeOsamu OharaMasaru TaniguchiPublished in: Nature immunology (2017)
Although invariant Vα14+ natural killer T cells (NKT cells) are thought to be generated from CD4+CD8+ double-positive (DP) thymocytes, the developmental origin of CD4-CD8- double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (TH1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor in determining the functional properties of NKT cells.
Keyphrases
- induced apoptosis
- cell cycle arrest
- endoplasmic reticulum stress
- signaling pathway
- type diabetes
- poor prognosis
- metabolic syndrome
- gene expression
- oxidative stress
- squamous cell carcinoma
- immune response
- dna methylation
- radiation therapy
- copy number
- mass spectrometry
- insulin resistance
- binding protein
- adipose tissue
- genome wide
- dendritic cells
- rectal cancer
- locally advanced
- long non coding rna