Eric Vivier

Publications (126)1338.65 Total impact

• Article: [Natural killer cells: adaptation and memory in innate immunity].

  Emilie Narni-Mancinelli, Sophie Ugolini, Eric Vivier
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  ABSTRACT: Natural killer (NK) cells are lymphocytes of the innate immune system that can kill tumor and infected cells. NK cells also secrete cytokines that participate in the shaping of the adaptive immune response. During the past few years, several studies have shown that the threshold of NK cell responsiveness is more adaptable than originally thought. NK cell reactivity is tuned by the environment and depends on the time of exposure of NK cells to their microenvironment. The impact of the NK cell response on immunity also depends on the intensity and the nature of the tumor or infections assaults. We review here how the local context impacts on NK cell responsiveness and shapes the outcome of NK cell activation.
  Medecine sciences: M/S 04/2013; 29(4):389-95. · 0.64 Impact Factor
• Article: Innate lymphoid cells - a proposal for uniform nomenclature.

  Hergen Spits, David Artis, Marco Colonna, Andreas Diefenbach, James P Di Santo, Gerard Eberl, Shigeo Koyasu, Richard M Locksley, Andrew N J McKenzie, Reina E Mebius, Fiona Powrie, Eric Vivier
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  ABSTRACT: Innate lymphoid cells (ILCs) are a family of developmentally related cells that are involved in immunity and in tissue development and remodelling. Recent research has identified several distinct members of this family. Confusingly, many different names have been used to characterize these newly identified ILC subsets. Here, we propose that ILCs should be categorized into three groups based on the cytokines that they can produce and the transcription factors that regulate their development and function.
  Nature Reviews Immunology 01/2013; 13(2):145-9. · 32.25 Impact Factor
• Article: Tuning the threshold of natural killer cell responses.

  Emilie Narni-Mancinelli, Sophie Ugolini, Eric Vivier
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  ABSTRACT: Natural killer cells are lymphocytes of the innate immune system that can kill an array of tumor and infected cells and secrete cytokines that participate in the shaping of the adaptive immune response. While it was believed that NK cell effector responses are acquired during maturation and then fixed, it appears that the threshold of NK cell responsiveness is more adaptable than originally thought. We review here how the local context provides several signals that impact on NK cell differentiation, responsiveness and shapes the antiviral and immunoregulatory outcome of NK cell activation.
  Current opinion in immunology 12/2012; · 10.88 Impact Factor
• Article: Differential responses of immune cells to type I interferon contribute to host resistance to viral infection.

  Thomas Baranek, Thien-Phong Vu Manh, Yannick Alexandre, Muhammad Ahmad Maqbool, Joaquin Zacarias Cabeza, Elena Tomasello, Karine Crozat, Gilles Bessou, Nicolas Zucchini, Scott H Robbins, Eric Vivier, Ulrich Kalinke, Pierre Ferrier, Marc Dalod
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  ABSTRACT: Type I interferons (IFNs) are central to antiviral defense, but how they orchestrate immune cell function is incompletely understood. We determined that IFNs produced during murine cytomegalovirus (MCMV) infection differentially affect dendritic cells (DCs) and natural killer (NK) cells. IFNs induce cell-intrinsic responses in DCs, activating antiproliferative, antiviral, and lymphocyte-activating gene networks, consistent with high activity of the transcription factor STAT1 in these cells. By comparison, NK cells exhibit lower STAT1 expression and reduced IFN responsiveness. Rather, IFNs indirectly affect NK cells by inducing IL-15, which activates the transcription factor E2F and stimulates genes promoting cell expansion. IFN cell-intrinsic responses are necessary in DCs, but not NK cells, for MCMV resistance. Thus, sensitivity to IFN-induced cytokines and differences in IFN receptor signaling program immune cells to mount distinct responses that promote viral control.
  Cell host & microbe 10/2012; 12(4):571-84. · 13.02 Impact Factor
• Article: Interferon-γ production by natural killer cells and cytomegalovirus in critically ill patients.

  Laurent Chiche, Jean-Marie Forel, Guillemette Thomas, Catherine Farnarier, Céline Cognet, Christophe Guervilly, Christine Zandotti, Frédéric Vély, Antoine Roch, Eric Vivier, Laurent Papazian
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  ABSTRACT: OBJECTIVE:: The mechanisms involved in cytomegalovirus reactivation in critically ill patients who were previously immunocompetent are still unknown. The current study was designed to evaluate the possible role of natural killer cells in the reactivation of cytomegalovirus in these patients. DESIGN:: Prospective observational. SETTING:: A medical intensive care unit of a university hospital. PATIENTS:: Fifty-one subjects, including 15 patients who experienced cytomegalovirus reactivation (cases) during their intensive care unit stay and 15 patients who matched intensive care unit controls, selected from a cohort of consecutive nonimmunocompromised intensive care unit patients, as well as healthy controls. INTERVENTIONS:: Tests included weekly systematic immunomonitoring and routine screening for cytomegalovirus infection until discharge from the intensive care unit or death. The immunophenotype and functions of natural killer cells were performed by flow cytometry, and serum levels of pro- and anti-inflammatory cytokines were determined by enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS:: The overall occurrence of cytomegalovirus reactivation in the cohort was 27%. No differences of natural killer cell effector functions were observed at admission between cases and controls. Instead, before cytomegalovirus reactivation, the ability of natural killer cells to secrete interferon-γ was significantly reduced in cases as compared with controls upon stimulation with antibody-coated target cells (p = .029) and with K562 cell stimulation (p = .029). No phenotypic or quantitative differences were observed between cases and controls. Cases exhibited higher levels of interleukin 10 (p = .031) and interleukin 15 (p = .021) than controls before cytomegalovirus reactivation. CONCLUSIONS:: Impaired natural killer cell function with reduced interferon-γ secretion precedes the occurrence of cytomegalovirus reactivation among previously immunocompetent critically ill patients.
  Critical care medicine 09/2012; · 6.37 Impact Factor
• Article: When NK cells overcome their lack of education.

  Baptiste N Jaeger, Eric Vivier
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  ABSTRACT: Cells of the immune system have evolved various molecular mechanisms to sense their environment and react to alterations of self. NK cells are lymphocytes with effector and regulatory functions, which are remarkably adaptable to changes in self. In a study published in this issue of the JCI, Tarek and colleagues report the clinical benefits of manipulating NK cell adaptation to self in an innovative mAb-based therapy against neuroblastoma (NB). This novel therapeutic strategy should stimulate further research on NK cell therapies.
  The Journal of clinical investigation 08/2012; 122(9):3053-6. · 15.39 Impact Factor
• Source

  Available from: Christine Bellanné-Chantelot

  Article: Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis.

  Baptiste N Jaeger, Jean Donadieu, Céline Cognet, Claire Bernat, Diana Ordoñez-Rueda, Vincent Barlogis, Nizar Mahlaoui, Aurore Fenis, Emilie Narni-Mancinelli, Blandine Beaupain, Christine Bellanné-Chantelot, Marc Bajénoff, Bernard Malissen, Marie Malissen, Eric Vivier, Sophie Ugolini
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  ABSTRACT: Natural killer (NK) cells are bone marrow (BM)-derived granular lymphocytes involved in immune defense against microbial infections and tumors. In an N-ethyl N-nitrosourea (ENU) mutagenesis strategy, we identified a mouse mutant with impaired NK cell reactivity both in vitro and in vivo. Dissection of this phenotype showed that mature neutrophils were required both in the BM and in the periphery for proper NK cell development. In mice lacking neutrophils, NK cells displayed hyperproliferation and poor survival and were blocked at an immature stage associated with hyporesponsiveness. The role of neutrophils as key regulators of NK cell functions was confirmed in patients with severe congenital neutropenia and autoimmune neutropenia. In addition to their direct antimicrobial activity, mature neutrophils are thus endowed with immunoregulatory functions that are conserved across species. These findings reveal novel types of cooperation between cells of the innate immune system and prompt examination of NK cell functional deficiency in patients suffering from neutropenia-associated diseases.
  Journal of Experimental Medicine 03/2012; 209(3):565-80. · 13.85 Impact Factor
• Article: Partial MCM4 deficiency in patients with growth retardation, adrenal insufficiency, and natural killer cell deficiency.

  Laure Gineau, Céline Cognet, Nihan Kara, Francis Peter Lach, Jean Dunne, Uma Veturi, Capucine Picard, Céline Trouillet, Céline Eidenschenk, Said Aoufouchi, Alexandre Alcaïs, Owen Smith, Frédéric Geissmann, Conleth Feighery, Laurent Abel, Agata Smogorzewska, Bruce Stillman, Eric Vivier, Jean-Laurent Casanova, Emmanuelle Jouanguy
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  ABSTRACT: Natural killer (NK) cells are circulating cytotoxic lymphocytes that exert potent and nonredundant antiviral activity and antitumoral activity in the mouse; however, their function in host defense in humans remains unclear. Here, we investigated 6 related patients with autosomal recessive growth retardation, adrenal insufficiency, and a selective NK cell deficiency characterized by a lack of the CD56(dim) NK subset. Using linkage analysis and fine mapping, we identified the disease-causing gene, MCM4, which encodes a component of the MCM2-7 helicase complex required for DNA replication. A splice-site mutation in the patients produced a frameshift, but the mutation was hypomorphic due to the creation of two new translation initiation methionine codons downstream of the premature termination codon. The patients' fibroblasts exhibited genomic instability, which was rescued by expression of WT MCM4. These data indicate that the patients' growth retardation and adrenal insufficiency likely reflect the ubiquitous but heterogeneous impact of the MCM4 mutation in various tissues. In addition, the specific loss of the NK CD56(dim) subset in patients was associated with a lower rate of NK CD56(bright) cell proliferation, and the maturation of NK CD56(bright) cells toward an NK CD56(dim) phenotype was tightly dependent on MCM4-dependent cell division. Thus, partial MCM4 deficiency results in a genetic syndrome of growth retardation with adrenal insufficiency and selective NK deficiency.
  The Journal of clinical investigation 03/2012; 122(3):821-32. · 15.39 Impact Factor
• Article: NK cell genesis: a trick of the trail.

  Emilie Narni-Mancinelli, Eric Vivier
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  ABSTRACT: In this issue of Immunity, Gordon et al. (2012) analyzed the role of the transcription factors T-bet and Eomesodermin in natural killer (NK) cell development, revealing a distinct spatiotemporal requirement of these factors for NK cell maturation.
  Immunity 01/2012; 36(1):1-3. · 21.64 Impact Factor
• Article: Tuning of natural killer cell reactivity by NKp46 and Helios calibrates T cell responses.

  Emilie Narni-Mancinelli, Baptiste N Jaeger, Claire Bernat, Aurore Fenis, Sam Kung, Aude De Gassart, Sajid Mahmood, Marta Gut, Simon C Heath, Jordi Estellé, Elodie Bertosio, Frédéric Vely, Louis N Gastinel, Bruce Beutler, Bernard Malissen, Marie Malissen, Ivo G Gut, Eric Vivier, Sophie Ugolini
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  ABSTRACT: Natural killer (NK) cells are lymphocytes involved in antimicrobial and antitumoral immune responses. Using N-ethyl-N-nitrosourea mutagenesis in mice, we identified a mutant with increased resistance to viral infections because of the presence of hyperresponsive NK cells. Whole-genome sequencing and functional analysis revealed a loss-of-function mutation in the Ncr1 gene encoding the activating receptor NKp46. The down-regulation of NK cell activity by NKp46 was associated with the silencing of the Helios transcription factor in NK cells. NKp46 was critical for the subsequent development of antiviral and antibacterial T cell responses, which suggests that the regulation of NK cell function by NKp46 allows for the optimal development of adaptive immune responses. NKp46 blockade enhanced NK cell reactivity in vivo, which could enable the design of immunostimulation strategies in humans.
  Science 01/2012; 335(6066):344-8. · 31.20 Impact Factor
• Article: NK cell MHC class I specific receptors (KIR): from biology to clinical intervention.

  Ariane Thielens, Eric Vivier, François Romagné
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  ABSTRACT: The natural killer (NK) cell effector response towards infected cells or tumoural cells is guided by the integration of activating and inhibitory signals sensed by NK cell surface receptors. Major histocompatibility complex class I specific inhibitory receptors expressed by NK cells have two distinct roles: while allowing self tolerance, they are also needed for the acquisition of NK cell functional competence, a process termed education. In the context of allotransplantation, NK cell alloreactivity, arising from the expression on donor NK cells of inhibitory killer Ig-like receptors (KIRs) that do not recognize human leukocyte antigen from the patient, has shown clinical benefit for leukaemia patients. Based on these genetic studies, a blocking antibody directed against KIRs, as well as allogeneic NK cell infusions are now tested in clinical trials in various oncology indications. They offer promising immunotherapeutic approaches for the treatment of cancer patients.
  Current opinion in immunology 01/2012; 24(2):239-45. · 10.88 Impact Factor
• Article: Mapping of NKp46(+) Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues.

  Elena Tomasello, Nadia Yessaad, Emilie Gregoire, Kelly Hudspeth, Carmelo Luci, Domenico Mavilio, Jean Hardwigsen, Eric Vivier
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  ABSTRACT: Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) transcription factor. Here, we documented the distribution and the phenotype of human NKp46(+) cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46(+) cells were found in splenic red pulp, in lymph nodes, in lungs, and gut lamina propria, thus mirroring mouse NKp46(+) cell distribution. We also identified a novel cell subset of CD56(dim)NKp46(low) cells that includes RORγt(+) ILCs with a lineage(-)CD94(-)CD117(bright)CD127(bright) phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.
  Frontiers in immunology. 01/2012; 3:344.
• Article: Phenotype and functions of natural killer cells in critically-ill septic patients.

  Jean-Marie Forel, Laurent Chiche, Guillemette Thomas, Julien Mancini, Catherine Farnarier, Céline Cognet, Christophe Guervilly, Aurélie Daumas, Frédéric Vély, François Xéridat, Eric Vivier, Laurent Papazian
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  ABSTRACT: Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models. We studied the phenotype and functions of circulating NK cells in critically-ill septic patients. Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry. The absolute number of peripheral blood CD3-CD56(+) NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3-70]%) compared to healthy controls (43.5[32.1-53.1]%) or Sepsis patients (49.2[37.3-62.9]%) (p = 0.002). Compared to healthy (10.2[6.3-13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2-9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1-54.7]%) compared to Sepsis patients (18.4[11.7-35.7]%, p<0.01) or healthy controls (26.8[19.3-44.9]%, p = 0.09) in ADCC condition. Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions. NTC00699868.
  PLoS ONE 01/2012; 7(12):e50446. · 4.09 Impact Factor
• Article: Targeting natural killer cells and natural killer T cells in cancer.

  Eric Vivier, Sophie Ugolini, Didier Blaise, Christian Chabannon, Laurent Brossay
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  ABSTRACT: Natural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.
  Nature Reviews Immunology 01/2012; 12(4):239-52. · 32.25 Impact Factor
• Article: Protection from inflammatory organ damage in a murine model of hemophagocytic lymphohistiocytosis using treatment with IL-18 binding protein.

  Laura Chiossone, Sandra Audonnet, Bruno Chetaille, Lionel Chasson, Catherine Farnarier, Yael Berda-Haddad, Stefan Jordan, Ulrich H Koszinowski, Marc Dalod, Karin Mazodier, Daniela Novick, Charles A Dinarello, Eric Vivier, Gilles Kaplanski
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  ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition due to the association of an infectious agent with lymphocyte cytotoxicity defects, either of congenital genetic origin in children or presumably acquired in adults. In HLH patients, an excess of lymphocyte or macrophage cytokines, such as IFN-γ and TNFα is present in serum. In animal models of the disease, IFN-γ and TNF-α have been shown to play a central pathogenic role. In humans, unusually high concentrations of IL-18, an inducer of IFN-γ, and TNF-α have been reported, and are associated with an imbalance between IL-18 and its natural inhibitor IL-18 binding protein (IL-18BP) resulting in an excess of free IL-18. Here we studied whether IL-18BP could reduce disease severity in an animal model of HLH. Mouse cytomegalovirus infection in perforin-1 knock-out mice induced a lethal condition similar to human HLH characterized by cytopenia with marked inflammatory lesions in the liver and spleen as well as the presence of hemophagocytosis in bone marrow. IL-18BP treatment decreased hemophagocytosis and reversed liver as well as spleen damage. IL-18BP treatment also reduced both IFN-γ and TNF-α production by CD8(+) T and NK cells, as well as Fas ligand expression on NK cell surface. These data suggest that IL-18BP is beneficial in an animal model of HLH and in combination with anti-infectious therapy may be a promising strategy to treat HLH patients.
  Frontiers in immunology. 01/2012; 3:239.
• Article: Natural killer cell tolerance: control by self or self-control?

  Baptiste N Jaeger, Eric Vivier
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  ABSTRACT: A major challenge for the immune system is to control pathogens and stressed cells, such as infected or tumors cells, while sparing healthy self-cells. To achieve this tolerance to self, immune cells must recognize and differentiate "self" versus "nonself" and "self" versus "altered self." In the absence of self-tolerance, cells of the adaptive immune system attack healthy cells and cause autoimmune diseases such as lupus, psoriasis, and type I diabetes. Mechanisms at work to ensure tolerance in the innate immune system are still poorly understood. Natural killer cells are innate immune lymphocytes, which have the capacity to kill cellular targets and produce cytokines without prior specific sensitization. Because of these intrinsic effector capacities, tolerance mechanisms must exist to prevent autoreactivity. Herein, we will review the present knowledge on NK cell tolerance.
  Cold Spring Harbor perspectives in biology 01/2012; 4(3). · 9.40 Impact Factor
• Source

  Available from: Hervé Luche

  Article: Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor.

  Emilie Narni-Mancinelli, Julie Chaix, Aurore Fenis, Yann M Kerdiles, Nadia Yessaad, Ana Reynders, Claude Gregoire, Herve Luche, Sophie Ugolini, Elena Tomasello, Thierry Walzer, Eric Vivier
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  ABSTRACT: NKp46 is a cell surface receptor expressed on natural killer (NK) cells, on a minute subset of T cells, and on a population of innate lymphoid cells that produce IL-22 and express the transcription factor retinoid-related orphan receptor (ROR)-γt, referred to as NK cell receptor (NKR)(+)ROR-γt(+) cells. Here we describe Nkp46(iCre) knock-in mice in which the gene encoding the improved Cre (iCre) recombinase was inserted into the Nkp46 locus. This mouse was used to noninvasively trace cells expressing NKp46 in vivo. Fate mapping experiments demonstrated the stable expression of NKp46 on NK cells and allowed a reappraisal of the sequential steps of NK cell maturation. NKp46 genetic tracing also showed that gut NKR(+)ROR-γt(+) and NK cells represent two distinct lineages. In addition, the genetic heterogeneity of liver NK cells was evidenced. Finally, Nkp46(iCre) mice also represent a unique mouse model of conditional mutagenesis specifically in NKp46(+) cells, paving the way for further developments in the biology of NKp46(+) NK, T, and NKR(+)ROR-γt(+) cells.
  Proceedings of the National Academy of Sciences 11/2011; 108(45):18324-9. · 9.68 Impact Factor
• Article: B7-H6/NKp30 interaction: a mechanism of alerting NK cells against tumors.

  Tomonori Kaifu, Bertrand Escalière, Louis N Gastinel, Eric Vivier, Myriam Baratin
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  ABSTRACT: Natural killer (NK) cells are lymphocytes of the innate immune system that sense target cells through a panel of activating and inhibitory receptors. Together with NKG2D, the natural cytotoxicity receptors (NCRs) are major activating receptors involved in tumor cell detection. Although numerous NKG2D ligands have been identified, characterization of the molecules interacting with the NCRs is still incomplete. The identification of B7-H6 as a counter structure of the NCR NKp30 shed light on the molecular basis of NK cell immunosurveillance. We review here the current knowledge on NKp30 and B7-H6, and we discuss their potential role in anti-tumor immunity.
  Cellular and Molecular Life Sciences CMLS 08/2011; 68(21):3531-9. · 6.57 Impact Factor
• Article: The 'T-cell-ness' of NK cells: unexpected similarities between NK cells and T cells.

  Emilie Narni-Mancinelli, Eric Vivier, Yann M Kerdiles
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  ABSTRACT: NK cells are considered as prototypical innate immune cells. However, recent discoveries have tended to refine the dogmatic concepts of innate and adaptive immunity. In many ways, NK cells are highly related to T cells and represent the closest innate immune cell lineage to adaptive immune cell populations. Here, we review the relationships between NK cells and T cells and discuss the recently described cell-intrinsic-adaptive features of NK cells.
  International Immunology 07/2011; 23(7):427-31. · 3.41 Impact Factor
• Article: Identity, regulation and in vivo function of gut NKp46+RORγt+ and NKp46+RORγt- lymphoid cells.

  Ana Reynders, Nadia Yessaad, Thien-Phong Vu Manh, Marc Dalod, Aurore Fenis, Camille Aubry, Georgios Nikitas, Bertrand Escalière, Jean Christophe Renauld, Olivier Dussurget, Pascale Cossart, Marc Lecuit, Eric Vivier, Elena Tomasello
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  ABSTRACT: The gut is a major barrier against microbes and encloses various innate lymphoid cells (ILCs), including two subsets expressing the natural cytotoxicity receptor NKp46. A subset of NKp46(+) cells expresses retinoic acid receptor-related orphan receptor γt (RORγt) and produces IL-22, like lymphoid tissue inducer (LTi) cells. Other NKp46(+) cells lack RORγt and produce IFN-γ, like conventional Natural Killer (cNK) cells. The identity, the regulation and the in vivo functions of gut NKp46(+) ILCs largely remain to be unravelled. Using pan-genomic profiling, we showed here that small intestine (SI) NKp46(+)RORγt(-) ILCs correspond to SI NK cells. Conversely, we identified a transcriptional programme conserved in fetal LTi cells and adult SI NKp46(+)RORγt(+) and NKp46(-)RORγt(+) ILCs. We also demonstrated that the IL-1β/IL-1R1/MyD88 pathway, but not the commensal flora, drove IL-22 production by NKp46(+)RORγt(+) ILCs. Finally, oral Listeria monocytogenes infection induced IFN-γ production in SI NK and IL-22 production in NKp46(+)RORγt(+) ILCs, but only IFN-γ contributed to control bacteria dissemination. NKp46(+) ILC heterogeneity is thus associated with subset-specific transcriptional programmes and effector functions that govern their implication in gut innate immunity.
  The EMBO Journal 06/2011; 30(14):2934-47. · 9.20 Impact Factor