Abstract
Invariant natural killer T (iNKT) cells are a CD1d-restricted T cell population that can respond to lipid antigenic stimulation within minutes by secreting a wide variety of cytokines. This broad functional scope has placed iNKT cells at the frontlines of many kinds of immune responses. Although the diverse functional capacities of iNKT cells have long been acknowledged, only recently have distinct iNKT cell subsets, each with a marked functional predisposition, been appreciated. Furthermore, the subsets can frequently occupy distinct niches in different tissues and sometimes establish long-term tissue residency where they can impact homeostasis and respond quickly when they sense perturbations. In this review, we discuss the developmental origins of the iNKT cell subsets, their localization patterns, and detail what is known about how different subsets specifically influence their surroundings in conditions of steady and diseased states.
Highlights
Adaptive immunity has long been appreciated as a chief means through which various jawed vertebrates stave off infectious pathogens
About 14% of these genes code for transcription factors, some of which are implicated in influencing lineage diversification. These results suggest that a given DP precursor is capable of adopting various fates but only commits to one upon receiving specific cues [68]
Acquiring the moniker iNKT10 due to their ability to produce IL-10, these cells express low levels of promyelotic leukemia zinc finger (PLZF) and are dependent on the transcription factor E4BP4 for their functional competence [42]. These cells are thymically derived as they are absent in adipose tissues of athymic nude mice, they could not be identified in detectable numbers in the thymus of a WT mouse [42]
Summary
Adaptive immunity has long been appreciated as a chief means through which various jawed vertebrates stave off infectious pathogens. Stage 0 iNKT cells do not express any appreciable levels of transcripts coding for lineage-determining transcription factors, even at the single cell level [69] Instead, their transcriptomes are reminiscent of uncommitted DP cells having recently undergone positive selection, suggesting that commitment to a subset can be reinforced by cytokine receptor signaling, it is unlikely to be the original signal driving diversification. Acquiring the moniker iNKT10 due to their ability to produce IL-10, these cells express low levels of PLZF and are dependent on the transcription factor E4BP4 for their functional competence [42] These cells are thymically derived as they are absent in adipose tissues of athymic nude mice, they could not be identified in detectable numbers in the thymus of a WT mouse [42]. The immunoregulatory role that the iNKT10 subset plays in adipose tissue to prevent obesity-related illnesses could be due to direct secretion of IL-10 (and possibly IL-2) at steady state
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