A novel spleen-resident immature NK cell subset and its maturation in a T-bet-dependent manner
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE133950 | GEO | 2019/07/15
REPOSITORIES: GEO
Similar Datasets
Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. Liver NK 1.1+CD49+, liver NK 1.1+CD49-, spleen NK 1.1+ CD49- populations of NK cells were sorted with FACS pooling cells from individual mice to end up with ~100k cells for each samples. mRNA was derived from lysates using Invitrogen oligo-dT beads
2014-04-26 | E-GEOD-52043 | biostudies-arrayexpress
Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. Liver DX5-CD49+, liver DX5+CD49-, spleen DX5+ CD49- populations of NK cells were sorted with FACS pooling cells from individual mice to end up with ~100k cells for each samples. mRNA was derived from lysates using Invitrogen oligo-dT beads
2014-04-26 | E-GEOD-52045 | biostudies-arrayexpress
Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells.
2014-04-26 | GSE52045 | GEO
Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells.
2014-04-26 | GSE52043 | GEO
Project description:A novel spleen-resident immature NK cell subset and its maturation in a T-bet-dependent manner
| PRJNA553197 | ENA
Project description:Liver-resident NK (lrNK) cells have been studied in human as well as in mice. In the current study, we compared the transcriptome of three porcine NK cell populations: CD8αhigh cNK cells from peripheral blood, CD8αhigh NK cells isolated from the liver and the liver-specific CD8αdim NK cells using RNA-seq, to gain new insights in the biology of these cells. Overall, our data indicate that lrNK cells show an immature and anti-inflammatory phenotype. We also observed that the CD8αhigh NK cell population present in the liver appears to represent a population with an intermediate phenotype. While the transcriptome of these cells largely overlaps with that of cNK cells, they also express transcripts associated with liver residency, such as CXCR6.
2023-06-28 | GSE229497 | GEO
Project description:Residential natural killer cells in peripheral tissues (trNK) act as pioneering responders during infectious challenges, and thus have attracted increasing attention recently. However, their discrimination with conventional NK (cNK) cells is still problematical, limiting the further knowledge of this particular NK subgroup. Here, through an integrative transcriptome comparison of the two NK subgroups from different tissues, two genesets are defined to efficiently distinguish them. From these genesets, we have also discovered a fundamental difference of the two NK subgroups in activation. Transcriptomic profiling of trNK and cNK activated in vivo after MCMV infection and in vitro by PMA/ionomycin stimulation further confirms this difference, and reveals a particular role of chromatin landscape in regulating the trNK activation. Additionally, trNK and cNK respectively highly express IL-21R and IL-18R, indicating that their activation is differentially regulated by cytokine milieu. Indeed, IL-21 is particular critical in accessorily promoting trNK activation, while IL-18 mainly facilitates cNK activation. Further, IL-21 is found to direct transcriptome changes in activated trNK using a bunch of bifunctional transcription factors. Together, our study sheds light on the bona fide difference between trNK and cNK, which will enrich our understanding of their distinct functionalities during immune responses.
2023-01-30 | GSE223677 | 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 | GSE264696 | 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.
2024-06-28 | GSE264694 | GEO