Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional mechanisms [ATAC-seq]
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PROVIDER: PRJNA1103811 | ENA |
REPOSITORIES: ENA
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Project description:Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional mechanisms [scRNA-seq]
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Project description:Cytokines drive the formation of memory-like NK cell subsets via epigenetic rewiring and transcriptional mechanisms [CITE-seq]
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Project description:NK cells are innate lymphoid cells that protect the host against malignant and infected cells. Activation with the cytokines IL-12, IL-15, and IL-18 induces NK cells to differentiate into memory-like NK cells that have enhanced function compared to conventional NK (cNK) cells. However, mechanisms governing their biology and whether all cNK cells become memory-like are unclear. We identified that IL-12/15/18 activation results in two main fates: reprogramming into enriched memory-like (eML) or priming into effector (eff)cNK cells. eML NK cells have distinct epigenetics, phenotype, and enhanced function (IFNγ, cytotoxicity) compared to cNK and effcNK cells. In contrast, effcNK cells transcriptionally and epigenetically resemble cNK cells. Furthermore, we identify that within cNK cells CD56bright and CD56dim NK cells are the origin of distinct subsets of eML NK cells. Moreover, these two subsets of eML NK cells persist within patients receiving ML NK cell therapy for several months. Thus, IL-12/15/18 activation of NK cells results in multiple cell fates, with epigenetic and transcriptional mechanisms orchestrating eML NK cell differentiation and function. These mechanistic insights provide new strategies to enhance NK cellular therapy.
2024-06-28 | GSE264694 | GEO
Project description:NK cells are innate lymphoid cells that protect the host against malignant and infected cells. Activation with the cytokines IL-12, IL-15, and IL-18 induces NK cells to differentiate into memory-like NK cells that have enhanced function compared to conventional NK (cNK) cells. However, mechanisms governing their biology and whether all cNK cells become memory-like are unclear. We identified that IL-12/15/18 activation results in two main fates: reprogramming into enriched memory-like (eML) or priming into effector (eff)cNK cells. eML NK cells have distinct epigenetics, phenotype, and enhanced function (IFNγ, cytotoxicity) compared to cNK and effcNK cells. In contrast, effcNK cells transcriptionally and epigenetically resemble cNK cells. Furthermore, we identify that within cNK cells CD56bright and CD56dim NK cells are the origin of distinct subsets of eML NK cells. Moreover, these two subsets of eML NK cells persist within patients receiving ML NK cell therapy for several months. Thus, IL-12/15/18 activation of NK cells results in multiple cell fates, with epigenetic and transcriptional mechanisms orchestrating eML NK cell differentiation and function. These mechanistic insights provide new strategies to enhance NK cellular therapy.
2024-06-28 | GSE264693 | GEO
Project description:NK cells are innate lymphoid cells that protect the host against malignant and infected cells. Activation with the cytokines IL-12, IL-15, and IL-18 induces NK cells to differentiate into memory-like NK cells that have enhanced function compared to conventional NK (cNK) cells. However, mechanisms governing their biology and whether all cNK cells become memory-like are unclear. We identified that IL-12/15/18 activation results in two main fates: reprogramming into enriched memory-like (eML) or priming into effector (eff)cNK cells. eML NK cells have distinct epigenetics, phenotype, and enhanced function (IFNγ, cytotoxicity) compared to cNK and effcNK cells. In contrast, effcNK cells transcriptionally and epigenetically resemble cNK cells. Furthermore, we identify that within cNK cells CD56bright and CD56dim NK cells are the origin of distinct subsets of eML NK cells. Moreover, these two subsets of eML NK cells persist within patients receiving ML NK cell therapy for several months. Thus, IL-12/15/18 activation of NK cells results in multiple cell fates, with epigenetic and transcriptional mechanisms orchestrating eML NK cell differentiation and function. These mechanistic insights provide new strategies to enhance NK cellular therapy.
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Project description:NK cells are lymphocytes that provide a first defense against viral infections and cancer. They act (i) cytotoxic by killing virus-infected and tumorigenic cells and (ii) immune regulatory by releasing cytokines and chemokines. These innate immune cells are commonly further classified as CD56bright and CD56dim NK cells. Former studies confirmed immune regulatory CD56bright NK cells as progenitors of cytotoxic CD56dim NK cells. CD57 was previously described as T cell marker for senescence and terminal differentiation. Recent studies detected CD57+ and CD57- NK cells among the CD56dim NK cell population and suggested a fully mature developmental status for CD57+ NK cells. The recent NK cell maturation model includes CD34+ hematopoietic stem cells (HSC), which develop into CD56bright NK cells, later into CD56dimCD57- and finally into terminally maturated CD56dimCD57+ (1) (2) (3). The molecular mechanisms of human NK cell differentiation and maturation remain unknown to this date. We performed for the first time a proteomic analysis of these distinct developmental stages of human primary NK cells, isolated from overall 10 healthy human blood donors. CD56bright NK cells versusCD56dim and CD56dimCD57- versus CD56dimCD57+ NK cells were analyzed by using quantitative peptide sequencing, which revealed individual protein signatures (3400 proteins) of these different NK cell developmental stages. Notably, our data support the current NK cell differentiation model by highlighting both strong distinctions between CD56dim/bright NK cells and close relationships between CD57+/- NK cells on the proteomic level. Among the most prominent and conserved regulated proteins, we detected myosin IIa, Calvasculin and Calcyclin with very similar expression patterns. We investigated their sub-cellular localization and observed specific recruitment- and accumulation-events at the NK cell immunological synapse (NKIS) after NK activation.
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Project description:It is known that NK cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of four murine NK cell subsets distinguished by CD117 (c-kit), CD27 and CD11b expression. Gene expression was measured in NK cell subsets freshly sorted from murine C57Bl/6 splenocytes. Two to three different batches were analysed.
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Project description:Murine Cytomegalovirus (MCMV) infection leads to the activation of various immune cells, including dendritic cells (DCs) and Natural Killer (NK) cells. This activation is partly driven by innate cytokines including IFN-I, which are induced early after infection. The objective was to address the role of different innate cytokines in shaping DC subsets and NK cell responses, in particular the role of cell intrinsic responses to IFN-I. In order to decipher the specific impact of cell-intrinsic IFN-I on cell subsets, we performed a genome-wide expression analysis on CD45.1 WT and CD45.2 IFNAR-/- splenic conventional DC (cDC) subsets and NK cells isolated from C57BL/6 [CD45.1 WT / CD45.2 IFNAR-KO] mixed bone marow chimera mice. This study includes data from cDC subsets (CD8a and CD11b) and NK cells purified by flow cytometry sorting from the spleen of bone marrow chimera (BMC) mice, under steady-state or MCMV condition. Two independent replicates were made for each cell type, from two independent pools of spleens from uninfected or d1.5 MCMV-infected BMC 5-8 mice, and were hybridized on 3 separate batches of gene chips.
2012-10-17 | E-GEOD-39555 | biostudies-arrayexpress
Project description:It is known that NK cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of four murine NK cell subsets distinguished by CD117 (c-kit), CD27 and CD11b expression.
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Project description:It is known that natural killer (NK) cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of human NK cell subsets derived from peripheral blood, thymus and bone marrow. NK cell subpopulations were defined via expression of CD56 and CD16.
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