Abstract:
:Autophagy plays an important role in the regulation of autoimmune and autoinflammatory responses of the immune cells. Defective autophagy process is associated with various autoimmune and inflammatory diseases. Moreover, in many of these diseases, the therapeutic use of normal immunoglobulin G or intravenous immunoglobulin (IVIG), a pooled normal IgG preparation, is well documented. Therefore, we explored if IVIG immunotherapy exerts therapeutic benefits via induction of autophagy in the immune cells. Here we show that IVIG induces autophagy in peripheral blood mononuclear cells (PBMCs). Further dissection of this process revealed that IVIG-induced autophagy is restricted to inflammatory cells like monocytes, dendritic cells, and M1 macrophages but not in cells associated with Th2 immune response like M2 macrophages. IVIG induces autophagy by activating AMP-dependent protein kinase, beclin-1, class III phosphoinositide 3-kinase and p38 mitogen-activated protein kinase and by inhibiting mammalian target of rapamycin. Mechanistically, IVIG-induced autophagy is F(ab')2-dependent but sialylation independent, and requires endocytosis of IgG by innate cells. Inhibition of autophagy compromised the ability of IVIG to suppress the inflammatory cytokines in innate immune cells. Moreover, IVIG therapy in inflammatory myopathies such as dermatomyositis, antisynthetase syndrome and immune-mediated necrotizing myopathy induced autophagy in PBMCs and reduced inflammatory cytokines in the circulation, thus validating the translational importance of these results. Our data provide insight on how circulating normal immunoglobulins maintain immune homeostasis and explain in part the mechanism by which IVIG therapy benefits patients with autoimmune and inflammatory diseases.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Das M,Karnam A,Stephen-Victor E,Gilardin L,Bhatt B,Kumar Sharma V,Rambabu N,Patil V,Lecerf M,Käsermann F,Bruneval P,Narayanaswamy Balaji K,Benveniste O,Kaveri SV,Bayry Jdoi
10.1038/s41419-020-2249-ysubject
Has Abstractpub_date
2020-01-23 00:00:00pages
50issue
1issn
2041-4889pii
10.1038/s41419-020-2249-yjournal_volume
11pub_type
杂志文章abstract::Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have a fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. The abundance, ease and repeatable access to subcutaneous adipose tissue and the...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.344
更新日期:2014-08-21 00:00:00
abstract::Breast cancer is the most common cancer type in women. Long non-coding RNAs (lncRNAs) have been reported as potential new diagnostic markers, prognostic factors, and therapeutic targets in cancer. However, the specific roles and mechanisms of lncRNAs in breast cancer remain to be elucidated. Here we demonstrated the d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2557-2
更新日期:2020-05-07 00:00:00
abstract::HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome represents a life-threatening pregnancy disorder with high fetal and maternal mortality, but its underlying molecular mechanisms remain unknown. Although apoptosis has been implicated in HELLP syndrome, its pathogenic role remains largely unclear. In th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.408
更新日期:2013-10-24 00:00:00
abstract::The DEAD/DEAH box helicase 11 (DDX11) plays vital roles in regulating the initiation of DNA replication. However, its precise function and regulation in hepatocellular carcinoma (HCC) have never been reported yet. In the current study, we found that DDX11 was overexpressed in HCC tissues. High DDX11 expression was pos...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2478-0
更新日期:2020-04-24 00:00:00
abstract::Although it is becoming increasingly evident that maternal starvation during pregnancy can have permanent effects on a range of physiological processes in the offspring, scant information is available about the consequence of such condition for oogenesis and hence for lifetime reproductive success of progeny in mammal...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0492-2
更新日期:2018-05-01 00:00:00
abstract::Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer cell proliferation, and invasion, but how the premalignant stromal fibroblasts trigger epithelial changes remain unclear. We demonstrate that atypical ductal hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0133-1
更新日期:2018-01-26 00:00:00
abstract::Microglia serve as the innate immune cells of the central nervous system (CNS) by providing continuous surveillance of the CNS microenvironment and initiating defense mechanisms to protect CNS tissue. Upon injury, microglia transition into an activated state altering their transcriptional profile, transforming their m...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03084-7
更新日期:2020-10-23 00:00:00
abstract::Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03304-0
更新日期:2021-01-04 00:00:00
abstract::The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS-/-) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, inclu...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1951-0
更新日期:2019-09-24 00:00:00
abstract::Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer's disease, catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediates cellular K+ efflux as an early step in the apoptotic cascade. Sin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.529
更新日期:2014-12-11 00:00:00
abstract::Proton pump inhibitors (PPI) target tumour acidic pH and have an antineoplastic effect in melanoma. The PPI esomeprazole (ESOM) kills melanoma cells through a caspase-dependent pathway involving cytosolic acidification and alkalinization of tumour pH. In this paper, we further investigated the mechanisms of ESOM-induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.67
更新日期:2010-10-21 00:00:00
abstract::Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-β (Aβ) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2644-4
更新日期:2020-06-08 00:00:00
abstract::In renal cell carcinoma, transglutaminase 2 (TGase 2) crosslinks p53 in autophagosomes, resulting in p53 depletion and the tumor's evasion of apoptosis. Inhibition of TGase 2 stabilizes p53 and induces tumor cells to enter apoptosis. This study explored the mechanism of TGase 2-dependent p53 degradation. We found that...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.14
更新日期:2016-03-31 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::Dihydroartemisinin (DHA) and its analogs are reported to possess selective anticancer activity. Here, we reported a novel DHA derivative DHA-37 that exhibited more potent anticancer activity on the cells tested. Distinct from DHA-induced apoptosis, DHA-37 triggered excessive autophagic cell death, and became the main ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1006-y
更新日期:2018-10-15 00:00:00
abstract::The proapoptotic protein, prostate apoptosis response-4 (Par-4), acts as a tumor suppressor in prostate cancer cells. The serine/threonine kinase casein kinase 2 (CK2) has a well-reported role in prostate cancer resistance to apoptotic agents or anticancer drugs. However, the mechanistic understanding on how CK2 suppo...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.532
更新日期:2014-01-23 00:00:00
abstract::The sex-determining region Y (SRY)-box (SOX) family has a crucial role in carcinogenesis and cancer progression. However, the role of SOX12 and the mechanism by which it is dysregulated in colorectal cancer (CRC) remain unclear. Here we analyzed SOX12 expression patterns in two independent CRC cohorts (cohort I, n = 3...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1481-9
更新日期:2019-03-11 00:00:00
abstract::We previously reported that marchantin M (Mar) is an active agent to induce apoptosis in human prostate cancer (PCa), but the molecular mechanisms of action remain largely unknown. Here, we demonstrate that Mar potently inhibited chymotrypsin-like and peptidyl-glutamyl peptide-hydrolyzing activities of 20S proteasome ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2013.285
更新日期:2013-08-08 00:00:00
abstract::The aberrant expression of long noncoding RNAs (lncRNAs) has been reported frequently in specific cancers, including high-grade serous ovarian cancer (HGSOC). The purpose of the present study was to explore the clinical significance and underlying mechanisms of a significantly dysregulated lncRNA (NEAT1) in HGSOC. Our...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0908-z
更新日期:2018-08-28 00:00:00
abstract::The identification of specific drug targets guides the development of precise cancer treatments. Compared with oncogenes, tumor suppressor genes have been poorly studied in the treatment of breast cancer. We integrate the microRNA expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0128-y
更新日期:2018-01-24 00:00:00
abstract::Glioblastoma multiforme (GBM) are resistant to TNFα-induced apoptosis and blockade of TNFα-induced NF-κB activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF-κB activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.10
更新日期:2012-02-09 00:00:00
abstract::Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of adipocyte differentiation and has an important role in metabolic syndrome. Phosphorylation of the receptor's ligand-binding domain at serine 273 has been shown to change the expression of a large number of genes implicated in obesity. The d...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.74
更新日期:2011-08-11 00:00:00
abstract::Protein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose rev...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1349-z
更新日期:2019-01-25 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::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::The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.139
更新日期:2012-10-11 00:00:00
abstract::The nuclear localization signal (NLS) in kinesin-14 KIFC1 is associated with nuclear importins and Ran gradient, but detailed mechanism remains unknown. In this study, we found that KIFC1 proteins have specific transport characteristics during cell cycle. In the absence of KIFC1, cell cycle kinetics decrease significa...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1619-9
更新日期:2019-05-24 00:00:00
abstract::Enhanced SNHG1 (small nucleolar RNA host gene 1) expression has been found to play a critical role in the initiation and progression of hepatocellular carcinoma (HCC) with its detailed mechanism largely unknown. In this study, we show that SNHG1 promotes the HCC progression through epigenetically silencing CDKN1A and ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03031-6
更新日期:2020-10-02 00:00:00
abstract::The serine protease hepsin is frequently overexpressed in human prostate cancer (PCa) and is associated with matrix degradation and PCa progression in mice. Curiously, low expression of hepsin is associated with poor survival in different cancer types, and transgenic overexpression of hepsin leads to loss of viability...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1830-8
更新日期:2019-08-09 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