Abstract:
:Immune surveillance through Foxp3+ regulatory T cells plays a crucial role in bone homeostasis. Scurfy, the mouse model of autoimmune IPEX syndrome, bears a loss-of-function mutation in Foxp3 that leads to multi-organ inflammation. Herein, we report that scurfy mice exhibit severe bone loss mediated by accelerated osteoclastogenesis. Mechanistically, Foxp3 deficiency results in the upregulation of NF-κB in T helper cells through the loss of repressive Foxp3/NEMO interaction, thereby unleashing NF-κB-mediated over-production of pro-osteoclastogenic cytokines. Flow cytometry analysis shows marked increase in lin-Sca-1+c-kit+ hematopoietic stem cells (LSK HSCs) and granulocyte/macrophage progenitors (GMPs) in bone marrow of scurfy mice with corresponding exacerbated osteoclastogenic potential, implying that osteoclast progenitors are affected at a very primitive stage in this disorder. Scurfy LSK HSCs exhibit greater sensitivity to M-CSF and contain abundant PU.1+ Sf LSK HSCs compared with WT. Accordingly, genetic or pharmacological inhibition of M-CSF or mTOR signaling, but not IL-17 signaling, attenuates osteoclastogenesis and osteopenia in scurfy. Thus, our study suggests that Foxp3 deficiency leads to osteopenia owing to dysregulated NF-κB activity and subsequent cytokine-mediated hyper-proliferation of myeloid precursors, and positions the NF-κB pathway as a potential target for therapeutic intervention for this disorder.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Chen TH,Swarnkar G,Mbalaviele G,Abu-Amer Ydoi
10.1038/cddis.2015.87subject
Has Abstractpub_date
2015-04-16 00:00:00pages
e1723issn
2041-4889pii
cddis201587journal_volume
6pub_type
杂志文章abstract::SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergi...
journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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journal_title:Cell death & disease
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abstract::Chronic lymphocytic leukemia (CLL) can be divided into groups based on biomarkers of poor prognosis. The expression of the tyrosine kinase ZAP-70 (member of the Syk tyrosine kinase family) in CLL cells is associated with shorter overall survival in CLL patients. Currently, there is a lack of targeted therapies for pat...
journal_title:Cell death & disease
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abstract::Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berber...
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pub_type: 杂志文章,评审
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Tumor-associated macrophages (TAMs) represent potential targets for anticancer treatments as these cells play critical roles in tumor progression and frequently antagonize the response to treatments. TAMs are usually associated to an M2-like phenotype, characterized by anti-inflammatory and protumoral properties. This...
journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2018-06-27 00:00:00
abstract::Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The role of MGL in tumorigenesis remains to be fully elucidated. We have previously shown that MGL expression was reduced or absent in multiple human malignancies, and overexpression of MGL inhibited cancer cell growth. Here, we have generated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0188-z
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abstract::Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung aden...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Reactive oxygen species (ROS) accumulation are involved in noise- and ototoxic drug-induced hair cell loss, which is the major cause of hearing loss. Bmi1 is a member of the Polycomb protein family and has been reported to regulate mitochondrial function and ROS level in thymocytes and neurons. In this study, we repor...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.549
更新日期:2015-01-22 00:00:00
abstract::Inhibition of human mitochondrial peptide deformylase (HsPDF) depolarizes the mitochondrial membrane, reduces mitochondrial protein translation and causes apoptosis in Burkitt's lymphoma. We showed that HsPDF mRNA and protein levels were overexpressed in cancer cells and primary acute myeloid leukemia samples. Myc reg...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.112
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journal_title:Cell death & disease
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doi:10.1038/s41419-020-03041-4
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journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::The tumor suppressor p53 has critical roles in regulating lipid metabolism, but whether and how p53 regulates cardiolipin (CL) de novo biosynthesis is unknown. Here, we report that p53 physically interacts with histone deacetylase SIRT6 in vitro and in vivo, and this interaction increases following palmitic acid (PA) ...
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic al...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::We previously showed that injury by partial duct ligation (PDL) in adult mouse pancreas activates Neurogenin 3 (Ngn3)(+) progenitor cells that can differentiate to β cells ex vivo. Here we evaluate the role of Ngn3(+) cells in β cell expansion in situ. PDL not only induced doubling of the β cell volume but also increa...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Treating corneal endothelial diseases tends to be challenging as human corneal endothelial cells (CECs) do not proliferate in vivo. The pathogenesis or mechanisms underlying injured CECs need further studies. The abnormal expression of PAX6, which is an essential transcription factor for corneal homeostasis, exhibits ...
journal_title:Cell death & disease
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abstract::Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we conf...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::We sought to identify miRNAs that can efficiently induce apoptosis in ovarian cancer cells by overcoming BCL-X(L) and MCL1 anti-apoptotic activity, using combined computational and experimental approaches. We found that miR-491-5p efficiently induces apoptosis in IGROV1-R10 cells by directly inhibiting BCL-X(L) expres...
journal_title:Cell death & disease
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abstract::The emergence of drug resistant tumours that are able to escape cell death pose a major problem in the treatment of cancers. Tumours develop resistance to DNA-damaging chemotherapeutic agents by acquiring the ability to repair their DNA. Combination therapies that induce DNA damage and disrupt the DNA damage repair pr...
journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::CEMIP (for "Cell migration-inducing protein" also called KIAA1199 and Hybid for "Hyaluronan-binding protein") expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid ...
journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2019-02-04 00:00:00