Abstract
Vα24-invariant human natural killer T (NKT) cells comprise a unique subset of CD1d-restricted T cells with potent immune regulatory function and are involved in the development of a variety of human diseases. However, the lack of comprehensive molecular subset identities limits their objective classification and clinical application. Using unbiased single-cell RNA sequencing (scRNA-seq) of over 4000 unstimulated and 7000 stimulated human peripheral blood NKT cells, we identified four and five clusters of NKT cells from each NKT group, respectively. Our study uncovers multiple previously unrecognized NKT subsets with potential functional specificities, including a cluster of NKT cells with regulatory T cell property. Flow cytometry and Ingenuity Pathway Analysis confirmed the existence of these NKT populations and indicated the related functional capacities. Our study provides the unbiased and more comprehensive molecular identities of human NKT subsets, which will eventually lead the way to tailored therapies targeting selected NKT subsets.
Highlights
Natural killer T (NKT) cells constitute a unique but heterogeneous subset of immune cells that arise from CD4+CD8+ cortical thymocytes, and feature characteristics of both conventional T and natural killer (NK) cells
IL-23 is necessary for the terminal differentiation and inflammatory functions associated with T helper-17 cells (Th17)
NKT17 cells are very scarce in peripheral circulation and the majority of NKT17 cells seem to be tissue resident cells that can be found in lung tissue and lymph nodes (Lynch et al, 2015)
Summary
Natural killer T (NKT) cells constitute a unique but heterogeneous subset of immune cells that arise from CD4+CD8+ cortical thymocytes, and feature characteristics of both conventional T and natural killer (NK) cells. Like mouse NKT cells, human NKT cells can be divided into different functional subsets based on cytokine secretion specificities in different experiments and various conditions, such as Th1-like, Th2-like, Th17-like and Treg-like NKT cells (Lee et al, 2002; Moreira-Teixeira et al, 2012; Brennan et al, 2013). The classification of human NKT cells is likely to be biased by the limited information on the molecular bases for the differentiation and function of NKT cell subsets. Such biases, in turn, would limit the capability of the objective evaluation, classification and clinical application of human NKT cells
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