Abstract:
:Interferon gamma (IFNγ) is a key moderator of cell-mediated immunity with diverse, mainly pro-inflammatory actions on immunocytes and target tissue. Recent studies have shown it may enhance anti-tumor and antiviral effects of CD8 T cells. Here we investigate the mechanisms by which IFNγ mediates CD8 T-cell cytotoxic function. We show that in vivo, antigen-specific CD8 T cells that produce INFγ are necessary to effect rejection of skin grafts expressing OVA as a transgene in keratinocytes. The ability of CD8 T cells to produce IFNγ enhanced their ability to migrate to the site of antigen-presenting skin cells. By in vivo imaging, we show that CTL motility, particularly speed, during graft rejection was enhanced by locally available IFNγ. We then used a reductionist two-cell model of CTL effectors and keratinocyte targets to investigate the effects of locally available (paracrine) and CTL-producing (autocrine) IFNγ on the motility behavior and killing ability of the CTL. Using live-cell imaging by prolonged time-lapse microscopy of primary effector CD8 T cells and antigen-expressing primary keratinocyte targets, we show that CD8 T-cell cytotoxic function and motility is enhanced by locally available IFNγ. Conversely, deprivation of either autocrine or paracrine IFNγ, or blockade of IFNγ signaling to CTL markedly reduced their cytotoxic function, their kinematics, and effector cell survival. We conclude that in vitro and in vivo, autocrine production of IFNγ by CTL enhances their motility and promotes killing of primary target keratinocytes. The absolute need for local IFNγ to enable cytotoxic CD8 T-cell function is of significance for immunotherapy for chronic viral infection and for cancer.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Bhat P,Leggatt G,Waterhouse N,Frazer IHdoi
10.1038/cddis.2017.67subject
Has Abstractpub_date
2017-06-01 00:00:00pages
e2836issue
6issn
2041-4889pii
cddis201767journal_volume
8pub_type
杂志文章abstract::ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechan...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02912-0
更新日期:2020-08-22 00:00:00
abstract::Mammalian female fertility is limited by the number and quality of oocytes in the ovarian reserve. The number of oocytes is finite since all germ cells cease proliferation to become oocytes in fetal life. Moreover, 70-80% of the initial oocyte population is eliminated during fetal and neonatal development, restricting...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2019-x
更新日期:2019-10-17 00:00:00
abstract::Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03256-5
更新日期:2020-12-07 00:00:00
abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2(-/-) mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.298
更新日期:2015-12-03 00:00:00
abstract::Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and is also highly resistant to conventional chemotherapy treatments. In this study, we report that Longikaurin A (LK-A), an ent-kaurane diterpenoid isolated from the plant Isodon ternifolius, induced cell cycle arrest and apoptosis in hum...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.66
更新日期:2014-03-20 00:00:00
abstract::Mediators produced by the airway epithelium control the activation, recruitment, and survival of pulmonary dendritic cells (DC) that present antigen to CD4(+) T cells during the genesis and exacerbation of allergic asthma. The epithelial-derived acute phase protein, serum amyloid A (SAA), induces DC maturation and TH1...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.327
更新日期:2013-09-05 00:00:00
abstract::Glucocorticoids (GCs) are metabolic hormones with immunosuppressive effects that have proven effective drugs against childhood acute lymphoblastic leukemia (ALL). Yet, the role of metabolic reprogramming in GC-induced ALL cell death is poorly understood. GCs efficiently block glucose uptake and metabolism in ALL cells...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0625-7
更新日期:2018-08-28 00:00:00
abstract::DEP-domain containing mTOR-interacting protein (DEPTOR), a natural mTOR inhibitor, has essential roles in several processes, including cell growth, metabolism, apoptosis, and immunity. DEPTOR expression has been shown to be diversely controlled at transcriptional levels in cell- and context-specific manners. However, ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03185-3
更新日期:2020-11-12 00:00:00
abstract::Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0015-6
更新日期:2017-12-13 00:00:00
abstract::Mitochondrial dysfunction and synaptic damage are critical early features of Alzheimer's disease (AD) associated with amyloid β (Aβ) and τ. We previously reported that the scaffolding protein RanBP9, which is overall increased in AD, simultaneously promotes Aβ generation and focal adhesion disruption by accelerating t...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.203
更新日期:2013-01-24 00:00:00
abstract::Bone marrow mesenchymal stem cells (MSCs) have demonstrated therapeutic effects for colitis through immunomodulation and anti-inflammation. However, whether MSC-derived exosomes possessed the similar function remains unclear. In present study, exosomes were isolated from control and IFN-γ-primed MSCs and was verified ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02788-0
更新日期:2020-07-30 00:00:00
abstract::Bevacizumab in neoadjuvant therapy provides a new hope of improved survival for patients with triple-negative breast cancer (TNBC) by targeting vascular endothelial growth factor in combination with chemotherapy, but curative effect is limited by bevacizumab's continuous use while mechanisms remain incompletely unders...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03161-x
更新日期:2020-11-19 00:00:00
abstract::Since publication of this paper, the authors have noticed that there were errors in Fig. 2A (the GAPDH of Mel-CV, Mel-CV.S, Mel-RMu and Mel-RMu.S), Fig. 2C (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3F (the GAPDH of Mel-CV.S and Mel-RMu.S), Fig. 3J(the GAPDH of Mel-RMu.S), Fig. 5C (the ERK1/2 of patient#3(post)), and...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-019-1301-2
更新日期:2019-03-05 00:00:00
abstract::The 37/67 kDa laminin receptor (LAMR) is a multifunctional protein, acting as an extracellular receptor, localizing to the nucleus, and playing roles in rRNA processing and ribosome assembly. LAMR is important for cell viability; however, it is unclear which of its functions are essential. We developed a silent mutant...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.19
更新日期:2010-01-01 00:00:00
abstract::Human glioma-associated mesenchymal stem cells (gbMSCs) are the stromal cell components that contribute to the tumourigenesis of malignant gliomas. Recent studies have shown that gbMSCs consist of two distinct subpopulations (CD90+ and CD90- gbMSCs). However, the different roles in glioma progression have not been exp...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1140-6
更新日期:2018-10-27 00:00:00
abstract::Glioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM ki...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1293-3
更新日期:2019-01-18 00:00:00
abstract::New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1915-4
更新日期:2019-10-31 00:00:00
abstract::During reproductive life, the mammary epithelium undergoes consecutive cycles of proliferation, differentiation and apoptosis. Doing so relies on the retained proliferative capacity, prolonged lifespan and developmental potency of mammary stem cells (MaSCs). ΔNp63α, the predominant TP63 isoform in mammary epithelia, i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.37
更新日期:2013-02-28 00:00:00
abstract::Characterized by their slow adhering property, skeletal muscle myogenic progenitor cells (MPCs) have been widely utilized in skeletal muscle tissue engineering for muscle regeneration, but with limited efficacy. Skeletal muscle regeneration is regulated by various cell types, including a large number of rapidly adheri...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1647-5
更新日期:2019-06-03 00:00:00
abstract::Cellular senescence is an initial barrier to tumor development that prevents the proliferation of premalignant cells. However, some of the features of senescent cells seem to promote tumor progression via senescence-associated secretory phenotype (SASP). Here, we demonstrated that the protein level of forkhead box Q1 ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.340
更新日期:2017-07-20 00:00:00
abstract::WD repeat protein 79 (WDR79) is a member of the WD-repeat protein family and functions as a scaffold protein during telomerase assembly, Cajal body formation and DNA double strand break repair. We have previously shown that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung ca...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.162
更新日期:2017-04-13 00:00:00
abstract::Triple-negative breast cancers (TNBCs) are aggressive forms of breast carcinoma associated with a high rate of recidivism. In this paper, we report the production of mammospheres from three lines of TNBC cells and demonstrate that both parthenolide (PN) and its soluble analog dimethylaminoparthenolide (DMAPT) suppress...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.94
更新日期:2016-04-14 00:00:00
abstract::The NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome is a multi-protein complex, aimed at producing IL-1β in response to danger signals which must be tightly regulated. Here we investigated the importance of the stress sensor, Heat Shock Protein 70 (HSP70) on NLRP3 inflammasome activation. H...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1491-7
更新日期:2019-03-15 00:00:00
abstract::Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacol...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.501
更新日期:2017-10-05 00:00:00
abstract::KLF5 is frequently deleted and downregulated in prostate cancer, and recently it has been reported that KLF5 loss is enriched in the aggressive branches of prostate cancer evolution. However, why KLF5 loss is associated with prostate cancer aggressiveness is still not clear. Herein, we analyzed KLF5 expression in TCGA...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2671-1
更新日期:2020-06-16 00:00:00
abstract::Alternatively activated macrophages have been reported to be helpful to alleviate systematic lupus erythematosus (SLE), and azithromycin could serve as an immunomodulator by promoting alternatively activated macrophage phenotype. However, the effect of azithromycin in SLE and the involved mechanism remain undetermined...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1097-5
更新日期:2018-10-22 00:00:00
abstract::Circular RNAs (circRNAs) have been shown to play critical roles in cancer biology, but their functions in nonalcoholic steatohepatitis (NASH) remain unexplored. Full length of circRNA_002581 was amplified and sequenced, followed by RNA immunoprecipitation, RNA-Fluorescence in Situ Hybridization and dual luciferase rep...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2293-7
更新日期:2020-02-13 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0628-4
更新日期:2018-05-29 00:00:00
abstract::Nicotinamide N-methyltransferase (NNMT, E.C. 2.1.1.1) N-methylates nicotinamide to produce 1-methylnicotinamide (MeN). We have previously shown that NNMT expression protected against neurotoxin-mediated cell death by increasing Complex I (CxI) activity, resulting in increased ATP synthesis. This was mediated via prote...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.200
更新日期:2013-06-13 00:00:00
abstract::Chronic hyperglycemia causes a progressive decrease of β-cell function and mass in type 2 diabetic patients. Growing evidence suggests that augment of autophagy may be an effective approach to protect β cells against various extra-/intracellular stimuli. In this study, we thus investigated whether bone marrow-derived ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.230
更新日期:2015-09-17 00:00:00