Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection

Helden, Mary J. van; Goossens, Steven; Daussy, Christophe; Mathieu, Anne-Laure; Faure, Fabrice; Marçais, Antoine; Vandamme, Niels; Farla, Natalie; Mayol, Katia; Viel, Sébastien; Degouve, Sophie; Debien, Emilie; Seuntjens, Eve; Conidi, Andrea; Chaix, Julie; Mangeot, Philippe; Bernard, Simon; Buffat, Laurent; Haigh, Jody J.; Huylebroeck, Danny; Lambrecht, Bart; Berx, Geert; Walzer, Thierry

doi:10.1083/jcb.2113oia260

Cited by 30 publications

(50 citation statements)

References 18 publications

(20 reference statements)

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“…B). Overexpression of Zeb2 in T‐bet deficient mice partially restored NK cell maturation, suggesting that some of the roles attributed to T‐bet may be indirectly mediated via Zeb2 . Blimp1 may also be part of the T‐bet network, as a previous study identified that this TF is downstream of T‐bet .…”

Section: Introductionmentioning

confidence: 91%

“…Consistently, CD122 hi NKp and a few NK cells are present in mice deficient for both Eomes and T‐bet . However, T‐bet and Eomes are essential for correct regulation of CD122 in mature NK cells in which CD122 expression is higher in T‐bet deficient NK cells, along with Eomes . Since CD122 expression is a rate‐limiting factor for the use of IL‐15, it seems that Eomes might be particularly important to promote NK cell proliferation via the induction of CD122, which would explain why there are so few peripheral NK cells in the absence of Eomes.…”

Section: Introductionmentioning

confidence: 93%

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T‐bet and Eomes govern differentiation and function of mouse and human NK cells and ILC1

et al. 2018

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T-bet and Eomes are T-box transcription factors that drive the differentiation and function of cytotoxic lymphocytes such as NK cells. Their DNA-binding domains are highly similar, suggesting redundant transcriptional activity. However, while these transcription factors have different patterns of expression, the phenotype of loss-of-function mouse models suggests that they play distinct roles in the development of NK cells and other innate lymphoid cells (ILCs). Recent technological advances using reporter mice and conditional knockouts were fundamental in defining the regulation and function of these factors at steady state and during pathological conditions such as various types of cancer or infection. Here, we review these recent developments, focusing on NK cells as prototypical cytotoxic lymphocytes and their development, and also discuss parallels between NK cells and T cells. We also examine the role of T-bet and Eomes in human NK cells and ILC1s. Considering divergent findings on mouse and human ILC1s, we propose that NK cells are defined by coexpression of T-bet and Eomes, while ILC1s express only one of these factors, either T-bet or Eomes, depending on the tissue or the species.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

T‐bet and Eomes govern differentiation and function of mouse and human NK cells and ILC1

et al. 2018

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“…Recent studies have harnessed the power of high‐throughput sequencing platforms to define the global changes in transcription and chromatin accessibility that occur in Ly49H + NK cells during the course of MCMV infection. A key finding of these studies was that memory NK cells and memory CD8 + T cells share a common transcriptional and epigenetic signature, and many of the regulated genes such as Tcf7 , Zeb2 , and Tox have known roles in NK cell development . Moreover, open chromatin regions in memory cells were enriched for binding sites for AP‐1 and underrepresented for TCF‐LEF binding sites, presenting novel pathways that may be involved in memory NK cell formation and/or maintenance …”

Section: Transcription Factors That Regulate Effector and Memory Nk Cmentioning

confidence: 99%

Transcriptional control of natural killer cell differentiation

Brillantes

Beaulieu

2018

Immunology

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Summary Natural killer (NK) cells are highly specialized cytotoxic lymphocytes that provide protection against pathogens and malignant cells. They develop from common lymphoid progenitors via a multi‐stage lineage commitment and differentiation process that gives rise to mature NK cells with potent cytotoxic functionality. Although generally considered cells of the innate immune system, recent studies have demonstrated that NK cells have the capacity to mount immune responses with features of adaptive immunity, including robust antigen‐specific clonal‐like expansion and the generation of long‐lived memory cells that mediate enhanced recall responses. Here, we discuss specific transcription factors that have been shown to commonly and uniquely regulate NK cell development and effector and memory responses in experimental mouse models.

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“…Critical extracellular signals influencing ILC functions and mediating ILC plasticity are depicted. Networks were designed based on Ch IP data or reporter assays (thick lines) together with gene deletion or overexpression systems (regular lines) . Nonexpressed genes are depicted in gray.…”

Section: Innate Lymphoid Cell Subsetsmentioning

confidence: 99%

Deconstructing deployment of the innate immune lymphocyte army for barrier homeostasis and protection

Almeida

Jacquelot

Belz

2018

Immunological Reviews

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Summary The study of the immune system has shifted from a purely dichotomous separation between the innate and adaptive arms to one that is now highly complex and reshaping our ideas of how steady‐state health is assured. It is now clear that immune cells do not neatly fit into these two streams and immune homeostasis depends on continual dialogue between multiple lineages of the innate (including dendritic cells, innate lymphoid cells, and unconventional lymphocytes) and adaptive (T and B lymphocytes) arms together with a finely tuned synergy between the host and microbes which is essential to ensure immune homeostasis. Innate lymphoid cells are critical players in this new landscape. Here, we discuss recent studies that have elucidated in detail the development of ILC s from their earliest progenitors and examine factors that influence their identification and ability to drive immune homeostasis and long‐term immune protection.

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Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection

Cited by 30 publications

References 18 publications

T‐bet and Eomes govern differentiation and function of mouse and human NK cells and ILC1

T‐bet and Eomes govern differentiation and function of mouse and human NK cells and ILC1

Transcriptional control of natural killer cell differentiation

Deconstructing deployment of the innate immune lymphocyte army for barrier homeostasis and protection

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