Functions of natural killer cells

Vivier, Éric; Tomasello, Elena; Baratin, Myriam; Walzer, Thierry; Ugolini, Sophie

doi:10.1038/ni1582

Cited by 3,237 publications

(3,143 citation statements)

References 108 publications

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“…1d). NK cells have disparate phenotypes according to their activation status and functionality; one model suggests that CD56hi CD16− NK cells are non‐activated NK cells that can even exert regulatory functions (IL‐10 production), CD56hi CD16± cells are recently activated cells in transition toward the fully activated effector phenotype (CD56lo CD16+) 12, 13, 14. In adherence to this model, we quantified the three different NK cell subtypes CD56hi CD16− NK cells, transitioning NK cells (CD56int CD16int), and effector NK (CD56lo CD16+) also did not reveal any statistically significant differences between the two patient groups (Fig.…”

Section: Resultsmentioning

confidence: 99%

Preeclampsia is Characterized by Fetal NK Cell Activation and a Reduction in Regulatory T Cells

Loewendorf

Nguyen

Yesayan

et al. 2015

American J Rep Immunol

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ProblemPreeclampsia affects 3–17% of pregnancies worldwide and has serious consequences for both the mother and the fetus. As maternal–fetal immune tolerance is bidirectional, fetal immunopathology may play a significant role in the pathogenesis of pregnancy disorders. Nevertheless, the impact of preeclampsia on the fetal immune system is unclear.Method of studyIn this case–control study, we examined the phenotype of innate and adaptive immune cells from the cord blood of 3rd trimester babies born to healthy mothers and compared them to cord blood from 3rd trimester babies born to mothers with symptomatic preeclampsia.ResultsThe ratio of CD56hi CD16− non‐activated/regulatory NK cells to CD56lo CD16+ activated/effector NK cells as well as the proportion of CD4+ T cells was significantly decreased in the cord blood of babies born to preeclamptic mothers. The percentage of FoxP3+ Treg, especially the FoxP3lo populations (resting Treg and cytokine Treg), were significantly reduced. Importantly, this reduction in FoxP3+ Treg affected the ratio of CD8+ effector T cells per FoxP3+ Treg in the cord blood of babies born to preeclamptic mothers.ConclusionThese observations indicate that there are significant fetal immune system derangements during preeclampsia.

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Section: Resultsmentioning

confidence: 99%

Preeclampsia is Characterized by Fetal NK Cell Activation and a Reduction in Regulatory T Cells

Loewendorf

Nguyen

Yesayan

et al. 2015

American J Rep Immunol

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“…1,2 The capacity to mediate these functions depends on the balance between inhibitory and activating signals. Activating receptors include the family of natural cytotoxicity receptors (NCRs) NKp46, NKp30 and NKp44.…”

Section: Introductionmentioning

confidence: 99%

A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets

et al. 2018

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NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCRB6C14R strain. Ly5.1C14R NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1C14R mice had normal number of NK cells, they showed an increased number of early maturation stage NK cells. CD49a+ILC1s were also increased but these cells lacked the expression of TRAIL. ILC3s that expressed NKp46 were not detectable and were not apparent when examined by T-bet expression. Thus, the C14R mutation reveals that NKp46 is important for NK cell and ILC differentiation, maturation and function.SignificanceInnate lymphoid cells (ILCs) play important roles in immune protection. Various subsets of ILCs express the activating receptor NKp46 which is capable of recognizing pathogen derived and tumor ligands and is necessary for immune protection. Here, we describe a spontaneous point mutation in the signal peptide of the NKp46 protein in congenic Ly5.1 mice which are widely used for tracking cells in vivo. This Ncr1 C14R mutation impairs NKp46 surface expression resulting in destabilization of Ncr1 and accumulation of NKp46 in the endoplasmic reticulum. Loss of stable NKp46 expression impaired the maturation of NKp46+ ILCs and altered the expression of TRAIL and T-bet in ILC1 and ILC3, respectively.

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“…Les cellules NK CD11b -sont localisées préférentiellement dans la moelle osseuse, les ganglions lymphatiques et le foie, et leur capacité Les cellules natural killer (NK) sont des lymphocytes de l'immunité innée qui jouent un rôle important dans les réponses antivirales et antitumorales ainsi que dans la défense contre les bactéries ou les parasites intracellulaires. Elles disposent de deux fonctions effectrices principales : la cytotoxicité et la production de cytokines [1]. Leur activité cytotoxique s'exerce contre des cellules reconnues comme cibles via un ensemble de récepteurs, activateurs ou inhibiteurs, et cette activité dépend de la libération de granules cytotoxiques contenant des protéines telles que la perforine ou les granzymes [2].…”

Section: Développement Et Maturation Des Cellules Nkunclassified

“…Cette désensibilisation est probablement due à la forte concentration de CXCL12 dans la moelle. La sortie des cellules NK de la moelle osseuse est donc dépendante 1 Aussi appelé SDF1 (stromal differentiation factor-1).…”

Section: Développement Et Maturation Des Cellules Nkunclassified