Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage

Pikovskaya, Olga; Chaix, Julie; Rothman, Nyanza J.; Collins, Amélie; Chen, Yen-Hua; Scipioni, Anna M.; Vivier, Éric; Reiner, Steven L.

doi:10.4049/jimmunol.1502396

Cited by 98 publications

(99 citation statements)

References 20 publications

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“…These cells were not liver‐specific, as they were also found in the spleen. A recent report proposed a bidirectional plasticity between cNKs and ILC1s that was mediated by the presence or absence of Eomesodermin (Eomes) . Our current findings suggest that this CD49a + DX5 + double‐positive cell population may be an intermediate population between cNK cells and ILC1s.…”

Section: Discussionsupporting

confidence: 53%

Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection

Souza-Fonseca-Guimarães

Rivera

et al. 2018

Clin & Trans Imm

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ObjectivesInnate lymphoid cells (ILCs) share many characteristics with CD4+ T cells, and group 1 ILCs share a requirement for T‐bet and the ability to produce IFNγ with T helper 1 (Th1) cells. Given this similarity, and the importance of Th1 cells for protection against intracellular protozoan parasites, we aimed to characterise the role of group 1 ILCs during Plasmodium infection.MethodsWe quantified group 1 ILCs in peripheral blood collected from subjects infected with with Plasmodium falciparum 3D7 as part of a controlled human malaria infection study, and in the liver and spleens of Pc AS‐infected mice. We used genetically‐modified mouse models, as well as cell‐depletion methods in mice to characterise the role of group 1 ILCs during Pc AS infection.ResultsIn a controlled human malaria infection study, we found that the frequencies of circulating ILC1s and NK cells decreased as infection progressed but recovered after volunteers were treated with antiparasitic drug. A similar observation was made for liver and splenic ILC1s in P. chabaudi chabaudi AS (Pc AS)‐infected mice. The decrease in mouse liver ILC1 frequencies was associated with increased apoptosis. We also identified a population of cells within the liver and spleen that expressed both ILC1 and NK cell markers, indicative of plasticity between these two cell lineages. Studies using genetic and cell‐depletion approaches indicated that group 1 ILCs have a limited role in antiparasitic immunity during Pc AS infection in mice.DiscussionOur results are consistent with a previous study indicating a limited role for natural killer (NK) cells during Plasmodium chabaudi infection in mice. Additionally, a recent study reported the redundancy of ILCs in humans with competent B and T cells. Nonetheless, our results do not rule out a role for group 1 ILCs in human malaria in endemic settings given that blood stage infection was initiated intravenously in our experimental models, and thus bypassed the liver stage of infection, which may influence the immune response during the blood stage.ConclusionOur results show that ILC1s are lost early during mouse and human malaria, and this observation may help to explain the limited role for these cells in controlling blood stage infection.

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Section: Discussionsupporting

confidence: 53%

Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection

Souza-Fonseca-Guimarães

Rivera

et al. 2018

Clin & Trans Imm

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“…Tissue‐resident ILC1s all express T‐bet at high levels and are presumably dependent on this factor for their development. As discussed above, transgenic expression of Eomes in ILC1s converts them at least in part into conventional NK cells . Reciprocally, transgenic expression of T‐bet promotes the development of ILC1s at the expense of NK cells in organs such as the BM, in which they normally do not develop.…”

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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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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“…NK cells express Eomes and Tbet, whereas ILC1s only express T-bet. Moreover, mice that lack Eomes in hematopoietic cells do not have NK cells but maintain ILC1s (Gordon et al, 2012; Klose et al, 2014; Pikovskaya et al, 2016). In contrast, T-bet deficient mice lack ILC1s and have significantly fewer NK cells in the spleen, lung, and liver, although NK cells are present in the BM and small intestine (Sojka et al, 2014b).…”

Section: Differential Requirements Of Ilc1s and Nk Cells For Eomes Anmentioning

confidence: 99%

Diversity and function of group 1 innate lymphoid cells

Cortez

Colonna

2016

Immunology Letters

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Innate lymphoid cells (ILCs) are a heterogeneous population of cells with diverse roles in immune responses. Three major groups of ILCs have been defined on the basis of similarity in their production of signature cytokines, developmental requirements, and phenotypic markers. Group 1 ILCs produce IFN-γ, express the T-box transcription factors (TF) Eomesodermin (Eomes) and/or T-bet. Group 2 ILCs secrete IL-5 and IL-13, express the TF GATA-3, and are identified by the expression of KLRG1, the receptor IL-7 (IL7R, also known as CD127), and the receptor for IL-33 (IL33R). Finally, group 3 ILCs produce IL-22 and IL-17 and express the TF RORγt along with the cell surface receptors CD127, NKp46, and CCR6. In this review, we will briefly overview each group in terms of phenotype, function and development and then focus more extensively on group 1 ILCs, expanding on their emerging diversity, their disparate functions and the differences between NK cells and ILC1.

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Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage

Cited by 98 publications

References 20 publications

Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection

Rapid loss of group 1 innate lymphoid cells during blood stage Plasmodium infection

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

Diversity and function of group 1 innate lymphoid cells

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