Human-induced CD49a+ NK cells promote fetal growth
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA765937 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16039616_1.fastq.gz | Fastqsanger.gz | |||
| SRR16039616_2.fastq.gz | Fastqsanger.gz | |||
| SRR16039617_1.fastq.gz | Fastqsanger.gz | |||
| SRR16039617_2.fastq.gz | Fastqsanger.gz | |||
| SRR16039618_1.fastq.gz | Fastqsanger.gz |
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Project description:CD49a+ natural killer (NK) cells are critical in promoting fetal development and maintaining immune tolerance at the maternal-fetal interface in early pregnancy. However, their tissue residency in human tissue hinder thorough studies and clinical application. How to induce functional human CD49a+ NK cells that could benefit pregnancy outcomes is still unknown. Here, we have established three no feeder cell induction systems to induce human CD49a+ NK cells from umbilical cord blood hematopoietic stem cells (HSCs), bone marrow HSCs or peripheral blood NK cells, respectively. These induced NK cells (iNKs) from three cell induction systems show high expression of CD49a, CD9, CD39, CD151, low expression of CD16, and no obvious cytotoxic capability, phenotypically and functionally similar with decidual NK cells. Furthermore, these iNKs also have high expression of growth-promoting factors and proangiogenic factors. Importantly, these iNKs have shown their capabilities to promote fetal growth and improve uterine artery blood flow in a murine pregnancy model in vivo. This research reveals properties of human-induced CD49a+ NK cells in promoting fetal growth from three cell induction systems, which may improve the feasibility of applying these iNKs to the patients having adverse pregnancy outcomes.
2022-02-23 | GSE184719 | GEO
Project description:Natural killer (NK) cells are present in large populations at the maternal-fetal interface during early pregnancy, but their roles in fetal growth are unclear. Here, we identify a CD49a+Eomes+ subset of NK cells that have the capability to secrete growth-promoting-factors (GPF), including pleiotrophin, osteoglycin and osteopontin in both humans and mice. Decreases in this GPF-secreting NK subset impair fetal development, and leads to fetal growth restriction. The transcriptional factor Nfil3 but not T-bet affects the function and the number of this decidual NK subset. The crosstalk of the HLA-G-ILT2-KIR2DL4 axis promotes the GPF-secreting function of this NK subset. Adoptive transfer of these induced CD49a+Eomes+NK cells can reverse the impaired fetal growth and rebuild an appropriate local microenvironment. These findings reveal new properties of NK cells in promoting fetal growth as well as novel approaches for therapeutically administering NK cells to reverse restricted nourishments within the microenvironment during early pregnancy. To investigate novel molecular signatures of human decidual NK cells, we performed microarray analysis on dNK cells (CD3−CD56+CD49a+CD49b−) and pNK cells (CD3−CD56+CD49a−CD49b+). dNK cells were purified from first-trimester deciduas. pNK cells were purified from adult peripheral blood mononuclear cells. Samples were collected from healthy adult donors after obtaining informed consent according to the Ethics Committee of the University of Science & Technology of China.
2018-01-04 | GSE97217 | GEO
Project description:Perfect fetal development is a solid foundation for successful fertility, in which the abundant natural killer (NK) cells in the decidua tissue at the maternal-fetal interface play an important role during the first trimester. The functional subsets and transcriptional regulation mechanisms of decidual NK (dNK) cells remain poorly understood. Here, we identified CD49a+PBX1+ dNK cells as a unique subset of NK cells that promote fetal development in both human and mice. PBX1 drove the transcription of key functional molecules pleiotrophin and osteoglycin that promote fetal development through direct promoter binding. In patients with unexplained recurrent spontaneous abortion (URSA), decreased expression of PBX1 and PBX1(G21S) mutation correlated with fetal growth restriction and pregnancy failure. Inactivation of Pbx1 in mouse NK cells caused impaired fetal development due to a decrease in growth promoting factors. Our observations reveal the molecular regulation mechanism of CD49a+PBX1+ dNK cells promoting fetal development, and indicate that impaired PBX1 in dNK cells may serve as pathogenesis and biomarker of URSA.
2021-01-01 | GSE110244 | GEO
Project description:CD49a+ and CD49a- NK cells from human livers
| PRJNA430421 | ENA
Project description:Purified NK cells from human liver tissues were first enriched by MACS using NK Cell Isolation Kit (Miltenyi Biotec, German) and CD49a+/- hepatic NK cells were isolated by FACS Aria cell sorter (BD Biosciences, United States) to attain a purity greater than 95%.
2020-07-07 | GSE109198 | GEO
Project description:Natural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy. Time series (4 hr, 16 hr, 64 hr) of NK cells treated with agonist (anti-CD158d mAb) or control. NK cells were from 4 donors.
2012-12-03 | E-GEOD-35330 | biostudies-arrayexpress
Project description:Quantification of proteins in the pancreas of fetal growth restriction.
2022-06-07 | PXD026502 | JPOST Repository
Project description:Human lung tissue-resident NK cells (trNK cells) are likely to play important roles in viral infections, inflammation and cancer. However, knowledge about lung trNK cells is lacking but is fundamental for exploiting these cells in therapeutic approaches. Here we analysed the transcriptome of CD69+CD49a+CD103+CD16-CD56bright, CD69+CD49a+CD103-CD16-CD56bright, CD69+CD49a-CD103-CD16-CD56bright, CD69-CD49a-CD103-CD16-CD56bright, and CD56dimCD16+NKG2A+CD57- NK cells isolated from human lung.
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Project description:Adaptive features of natural killer (NK) cells have been reported in various species with different underlying mechanisms. It is unclear, however, which NK cell populations are capable of mounting antigen-specific recall responses, and how such functions are regulated at the molecular level. Here we identify and characterize a discrete population of CD49a+CD16- NK cells in the human liver that display increased epigenetic potential to elicit memory responses and has the functional properties to exert antigen-specific immunity on the skin as an effector site. Integrated chromatin-based epigenetic and transcriptomic profiling revealed unique characteristics of hepatic CD49a+CD16- NK cells when compared to conventional CD49a-CD16+ NK cells thereby defining active genomic regions and molecules underpinning distinct NK cell reactivity. In contrast to conventional NK cells, our results suggest adaptive CD49a+CD16- NK cells to be able to bypass the KIR receptor-ligand system upon antigen-specific stimulation. Furthermore, these cells were highly migratory towards chemokine gradients expressed in epicutaneous patch test lesions as an effector site of adaptive immune responses of the skin. These results define pathways operative in human antigen-specific memory NK cells and provide a roadmap for harnessing this NK cell subset for specific therapeutic or prophylactic vaccine strategies.
2020-10-15 | GSE158485 | GEO
Project description:Characterisation of NKG2C+KIR+ tissue-resident NK cells in human lung and CD49a+ CD56bright NK cells in human blood.
2021-03-24 | GSE166654 | GEO