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Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells (part 2)

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE52045 | GEO | 2014/04/26

SECONDARY ACCESSION(S): PRJNA226586

REPOSITORIES: GEO

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Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells (part 1)

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

Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells (part 2)

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

Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells (part 1)

2014-04-26 | GSE52043 | GEO

Circulating NK cells establish tissue-residency upon acute infection of skin and mediate accelerated effector responses to secondary infection

Project description:Natural killer (NK) cells are present in the circulation and can also be found residing in tissues; these populations exhibit distinct developmental requirements and are thought to differ in terms of ontogeny. Here, we investigated whether circulating conventional NK (cNK) cells can develop into long-lived, tissue-resident cells following acute infections. We found that viral and bacterial infections of the skin triggered the recruitment of cNK cells and their differentiation into Tcf1hiCD69hi tissue-resident (trNK) cells that share transcriptional similarity with CD56brightTCF1hi NK cells in human tissues. Skin trNK arose from IFN--producing effector cells and required restricted expression of the transcriptional regulator Blimp1 to optimize Tcf1-dependent trNK formation. Upon secondary infection, trNK cells rapidly gained effector function and mediated an accelerated NK cell response. Thus, cNK cells redistribute and permanently position at sites of previous infection via a mechanism promoting tissueresidency that is distinct from Hobit-dependent developmental paths of NK cells and ILC1 seeding tissues during ontogeny.

2023-12-28 | GSE242313 | GEO

Circulating NK cells establish tissue-residency upon acute infection of skin and mediate accelerated effector responses to secondary infection

2023-12-28 | GSE227801 | GEO

Circulating NK cells establish tissue-residency upon acute infection of skin and mediate accelerated effector responses to secondary infection

Project description:Natural killer (NK) cells are present in the circulation and can also be found residing in tissues; these populations exhibit distinct developmental requirements and are thought to differ in terms of ontogeny. Here, we investigated whether circulating conventional NK (cNK) cells can develop into long-lived, tissue-resident cells following acute infections. We found that viral and bacterial infections of the skin triggered the recruitment of cNK cells and their differentiation into Tcf1hiCD69hi tissue-resident (trNK) cells that share transcriptional similarity with CD56brightTCF1hi NK cells in human tissues. Skin trNK arose from IFN-g-producing effector cells and required restricted expression of the transcriptional regulator Blimp1 to optimize Tcf1-dependent trNK formation. Upon secondary infection, trNK cells rapidly gained effector function and mediated an accelerated NK cell response. Thus, cNK cells redistribute and permanently position at sites of previous infection via a mechanism promoting tissueresidency that is distinct from Hobit-dependent developmental paths of NK cells and ILC1 seeding tissues during ontogeny

2023-12-28 | GSE226756 | GEO

Activation of tissue-resident NK and conventional NK are fundamentally different as indicated by their particular genesets

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

Comparative transcriptomics of porcine conventional blood NK cells, conventional liver NK cells and liver resident NK cells

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

Differential requirement for Nfil3 during NK cell development

Project description:Natural killer (NK) cells can be grouped into distinct subsets that are localized to different organs and exhibit different capacity to secrete cytokines and mediate cytotoxicity. Despite these hallmarks that reflect tissue-specific specialization in NK cells, little is known about the factors that control the development of these distinct subsets. The basic leucine zipper transcription factor nuclear factor interleukin 3 (Nfil3; E4bp4) is essential for bone marrow-derived NK cell development but it is not clear whether Nfil3 is equally important for all NK cell subsets nor how it induces NK lineage commitment. Here we show that Nfil3 is required for the formation of Eomesodermin (Eomes)-expressing NK cells, including conventional medullary and thymic NK cells, whereas TRAIL+ Eomes- NK cells develop independent of Nfil3. Loss of Nfil3 during the development of bone marrow-derived NK cells resulted in reduced expression of Eomes and, conversely, restoration of Eomes expression in Nfil3-/- progenitors rescued NK cell development and maturation. Collectively, these findings demonstrate that Nfil3 drives the formation of mature NK cell by inducing Eomes expression and reveal the differential requirements of NK cell subsets for Nfil3. RNA-sequencing of natural killer (NK) cell subsets

2014-05-07 | E-GEOD-54291 | biostudies-arrayexpress

Gene profiling of mouse liver NK and NKT cell subsets

Project description:This study shows that liver Eomes- NK cells are not precursors of classical Eomes+ NK cells but rather constitute a distinct lineage of innate lymphoid cells. Gene profile analyses show that Eomes- NK cells share part of their transcriptional program with NKT cells that includes genes involved in liver homing, NK cell receptors, and several cytokines and cytokine receptors. Eomes- NK cells, Eomes+ Nk cells and NKT cells were sorted by flow cytometry from Eomes-GFP reporter mice. Total RNA was extracted and hybridized to Affymetrix microarrays.

2014-01-29 | E-GEOD-53486 | biostudies-arrayexpress

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