Regulation of Development of CD56brightCD11c+ NK-like Cells with Helper Function by IL-18

Li, Wen; Okuda, A; Yamamoto, Hideyuki; Yamanishi, Kyosuke; Terada, Nobuyuki; Yamanishi, Hiromichi; Tanaka, Yoshimasa; Okamura, Haruki

doi:10.1371/journal.pone.0082586

Cited by 8 publications

(10 citation statements)

References 32 publications

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“…Cells sorted from KD OP9DLL1 co-cultures showed robust BCL11B knockdown (Figure 3b). Consistent with the association of CD1a expression with T-lineage commitment, control CD7+CD1a+ cells generated substantially lower numbers of NK (CD56+ and CD56+CD11c+ 37 ) and myeloid (CD33+ and CD14/15+) cells relative to those generated by control CD7+CD1a− cells (Figure 3c). These findings recapitulate the loss in alternative lineage potential seen with CD1a expression in primary thymic progenitors (Supplementary Figure 3a), validating the secondary cultures as an assay for investigating T-lineage commitment.…”

Section: Resultssupporting

confidence: 74%

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation

Luong

et al. 2017

Leukemia

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The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

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Section: Resultssupporting

confidence: 74%

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation

Luong

et al. 2017

Leukemia

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“…Therefore, the bottleneck for the development of γδT cell-mediated cancer therapy has been the lack of an established method suitable for the efficient and safe expansion of γδT cells. Recently, Okamura’s group reported a protocol to obtain high numbers of γδT cells using IL-18 [338,339,340,341]. The incubation of human PBMCs including 1%–2% γδT cells with γδT cell Ag and IL-2 and IL-18, induced the proliferation of γδT cells, but not αβT cells, by approximately several thousand-fold in a 2-week culture [338,339,340,341] (Figure 6A).…”

Section: Il-18 In Diseasementioning

confidence: 99%

Interleukin-18 in Health and Disease

Yasuda

Nakanishi

Tsutsui

2019

IJMS

389

288

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Interleukin (IL)-18 was originally discovered as a factor that enhanced IFN-γ production from anti-CD3-stimulated Th1 cells, especially in the presence of IL-12. Upon stimulation with Ag plus IL-12, naïve T cells develop into IL-18 receptor (IL-18R) expressing Th1 cells, which increase IFN-γ production in response to IL-18 stimulation. Therefore, IL-12 is a commitment factor that induces the development of Th1 cells. In contrast, IL-18 is a proinflammatory cytokine that facilitates type 1 responses. However, IL-18 without IL-12 but with IL-2, stimulates NK cells, CD4+ NKT cells, and established Th1 cells, to produce IL-3, IL-9, and IL-13. Furthermore, together with IL-3, IL-18 stimulates mast cells and basophils to produce IL-4, IL-13, and chemical mediators such as histamine. Therefore, IL-18 is a cytokine that stimulates various cell types and has pleiotropic functions. IL-18 is a member of the IL-1 family of cytokines. IL-18 demonstrates a unique function by binding to a specific receptor expressed on various types of cells. In this review article, we will focus on the unique features of IL-18 in health and disease in experimental animals and humans.

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“…57 Active caspase-1 catalyzes the proteolytic maturation of pro-IL-1b or pro-IL-18 resulting in the release of mature IL-1b or IL-18. There is growing evidence that inflammasome-generated IL-18 is crucial for the activation of innate lymphocytes including gd T cells in vitro [21][22][23]42,43,58,59 and in vivo. 24 In the present work, IL-18 by itself induced a pre-activated phenotype with increased CD25 expression and potently costimulated gd T-cell expansion in response to the various mevalonate-derived isoprenoid pyrophosphates.…”

Section: E953410-6mentioning

confidence: 99%

Stress-related and homeostatic cytokines regulate Vγ9Vδ2 T-cell surveillance of mevalonate metabolism

et al. 2014

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The potentially oncogenic mevalonate pathway provides building blocks for protein prenylation and induces cell proliferation and as such is an important therapeutic target. Among mevalonate metabolites, only isopentenyl pyrophosphate (IPP) has been considered to be an immunologically relevant antigen for primate-specific, innate-like Vg9Vd2 T cells with antitumor potential. We show here that Vg9Vd2 T cells pretreated with the stress-related, inflammasome-dependent cytokine interleukin 18 (IL-18) were potently activated not only by IPP but also by all downstream isoprenoid pyrophosphates that exhibit combined features of antigens and cell-extrinsic metabolic cues. Vg9Vd2 T cells induced this way effectively proliferated even under severe lymphopenic conditions and the antioxidant N-acetylcysteine significantly improved reconstitution of gd T cells predominantly with a central memory phenotype. The homeostatic cytokine IL-15 induced the differentiation of effector cells in an antigen-independent fashion, which rapidly produced abundant interferon g (IFNg) upon antigen re-encounter. IL-15 induced effector gd T cells displayed increased levels of the cytotoxic lymphocyte-associated proteins CD56, CD96, CD161 and perforin. In response to stimulation with isoprenoid pyrophosphates, these effector cells upregulated surface expression of CD107a and exhibited strong cytotoxicity against tumor cells in vitro. Our data clarify understanding of innate immunosurveillance mechanisms and will facilitate the controlled generation of robust Vg9Vd2 T cell subsets for effective cancer immunotherapy.

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Regulation of Development of CD56brightCD11c+ NK-like Cells with Helper Function by IL-18

Cited by 8 publications

References 32 publications

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation

Interleukin-18 in Health and Disease

Stress-related and homeostatic cytokines regulate Vγ9Vδ2 T-cell surveillance of mevalonate metabolism

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