Abstract:
:Skeletal health is maintained by bone remodeling, a process in which microscopic sites of effete or damaged bone are degraded on bone surfaces by osteoclasts and subsequently replaced by new bone, which is laid down by osteoblasts. This normal process can be disturbed in a variety of pathologic processes, including localized or generalized inflammation, metabolic and endocrine disorders, primary and metastatic cancers, and during aging as a result of low-grade chronic inflammation. Osteoclast formation and activity are promoted by factors, including cytokines, hormones, growth factors, and free radicals, and require expression of macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) by accessory cells in the bone marrow, including osteoblastic and immune cells. Expression of TNF receptor-associated factor 6 (TRAF6) is required in osteoclast precursors to mediate RANKL-induced activation of NF-κB, which is also necessary for osteoclast formation and activity. TRAF3, in contrast is not required for osteoclast formation, but it limits RANKL-induced osteoclast formation by promoting proteasomal degradation of NF-κB-inducing kinase in a complex with TRAF2 and cellular inhibitor of apoptosis proteins (cIAP). TRAF3 also limits osteoclast formation induced by TNF, which mediates inflammation and joint destruction in inflammatory diseases, including rheumatoid arthritis. Chloroquine and hydroxychloroquine, anti-inflammatory drugs used to treat rheumatoid arthritis, prevent TRAF3 degradation in osteoclast precursors and inhibit osteoclast formation in vitro. Chloroquine also inhibits bone destruction induced by ovariectomy and parathyroid hormone in mice in vivo. Mice genetically engineered to have TRAF3 deleted in osteoclast precursors and macrophages develop early onset osteoporosis, inflammation in multiple tissues, infections, and tumors, indicating that TRAF3 suppresses inflammation and tumors in myeloid cells. Mice with TRAF3 conditionally deleted in mesenchymal cells also develop early onset osteoporosis due to a combination of increased osteoclast formation and reduced osteoblast formation. TRAF3 protein levels decrease in bone and bone marrow during aging in mice and humans. Development of drugs to prevent TRAF3 degradation in immune and bone cells could be a novel therapeutic approach to prevent or reduce bone loss and the incidence of several common diseases associated with aging.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Boyce BF,Li J,Xing L,Yao Zdoi
10.3389/fimmu.2018.02263subject
Has Abstractpub_date
2018-09-28 00:00:00pages
2263issn
1664-3224journal_volume
9pub_type
杂志文章,评审abstract::For successful bone marrow transplantation (BMT), a preconditioning regime involving chemo and radiotherapy is used that results in DNA damage to both hematopoietic and stromal elements. Following radiation exposure, it is well recognized that a single wave of host-derived thymocytes reconstitutes the irradiated thymu...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01312
更新日期:2018-06-11 00:00:00
abstract::Vaccination is the most reliable measure to prevent infectious diseases in domestic animals. Development of novel vaccines demands extensive studies with new technologies, such as using novel adjuvants and immunomodulatory molecules. The co-stimulatory molecule 4-1BB provides a key signal that directs the fate of T ce...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01846
更新日期:2017-12-18 00:00:00
abstract:Background:The immune regulatory properties of semaphorin3A (sema3A) (both innate and adaptive) are well established in many in vitro studies. The injection of sema3A into a mice model of rheumatoid arthritis was proven to be highly beneficial, both in attenuating clinical symptoms and in decreasing inflammatory mechan...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00634
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02078
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abstract::Cell signaling is an essential requirement for mammalian cell invasion by Trypanosoma cruzi. Depending on the parasite strain and the parasite developmental form, distinct signaling pathways may be induced. In this short review, we focus on the data coming from studies with metacyclic trypomastigotes (MT) generated in...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00361
更新日期:2012-11-28 00:00:00
abstract::Corticosterone (CORT), a critical mediator of the hypothalamus pituitary adrenal axis in rodents, is a stress hormone that is classically viewed as possessing immune-suppressive properties. CORT is now appreciated to also mediate the neuroimmune-priming effect of stress to innate-immune stimulation, and hence serves a...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00003
更新日期:2018-01-22 00:00:00
abstract::In the setting of myocardial infarction (MI), ischemia reperfusion injury (IRI) occurs due to occlusion (ischemia) and subsequent re-establishment of blood flow (reperfusion) of a coronary artery. A similar phenomenon is observed in heart transplantation (HTx) when, after cold storage, the donor heart is connected to ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.599511
更新日期:2020-12-08 00:00:00
abstract::Leprosy, a disease caused by the intracellular parasite Mycobacterium leprae or Mycobacterium lepromatosis, has affected humans for more than 4,000 years and is a stigmatized disease even now. Since clinical manifestations of leprosy patients present as an immune-related spectrum, leprosy is regarded as an ideal model...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00567
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abstract::The emergence and continuous development of immune checkpoint inhibitors (ICIs) therapy brings a revolution in cancer therapy history, but the major hurdle associated with their usage is the concomitant ICIs-related toxicities that present a challenge for oncologists. The toxicities may involve non-specific symptoms o...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.02023
更新日期:2020-10-06 00:00:00
abstract::Protein kinase C isoform θ (PKCθ) is a key modulator of TCR signaling and mediates activation of NF-κB, NF-AT, and AP-1 transcription factors. Although in vitro studies of PKCθ(-/-) T cells have shown impaired activation responses, in vivo studies indicate that PKCθ requirement is not universal. While PKCθ is importan...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00259
更新日期:2012-08-14 00:00:00
abstract::One of the most significant challenges of cell biology is to understand how each type of cell copes with its specific workload without suffering damage. Among the most intriguing questions concerns intestinal epithelial cells in mammals; these cells act as a barrier between the internally protected region and the exte...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2013.00301
更新日期:2013-09-30 00:00:00
abstract::A 65-year-old Italian physician affected by Familial Mediterranean fever (FMF) was hospitalized due to progressive abdominal enlargement, which had begun 6 months before admission. Physical examination revealed ascites and bilateral leg edema. Abdominal CT scan showed ascitic fluid and extensive multiple peritoneal im...
journal_title:Frontiers in immunology
pub_type:
doi:10.3389/fimmu.2020.00889
更新日期:2020-05-13 00:00:00
abstract::Red blood cells (RBCs) have a well-defined lifespan, indicating a mechanism by which senescent cells of a certain age are removed from circulation. However, the specifics by which senescent cells are recognized and removed are poorly understood. There are multiple competing hypotheses for this process, perhaps the mos...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01425
更新日期:2017-10-30 00:00:00
abstract::Arginine methylation is a post-translational modification that regulates many biological processes. However, the role of arginine methylation in immune cells is not well studied. Here we report an essential role of protein arginine methyltransferase 5 (PRMT5) in T cell homeostasis and activation-induced expansion. Usi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00621
更新日期:2020-04-09 00:00:00
abstract::The Janus kinase 2 (JAK2)-driven myeloproliferative neoplasms (MPNs) are associated with clonal myelopoiesis, elevated risk of death due to thrombotic complications, and transformation to acute myeloid leukemia (AML). JAK2 inhibitors improve the quality of life for MPN patients, but these approved therapeutics do not ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.604142
更新日期:2020-11-30 00:00:00
abstract::Developing thymocytes interact sequentially with two distinct structures within the thymus: the cortex and medulla. Surviving single-positive and double-positive thymocytes from the cortex migrate into the medulla, where they interact with medullary thymic epithelial cells (mTECs). These cells ectopically express a va...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00352
更新日期:2015-07-14 00:00:00
abstract::Diseases due to mycobacteria, including tuberculosis, leprosy, and Buruli ulcer, rank among the top causes of death and disability worldwide. Animal studies have revealed the importance of T cells in controlling these infections. However, the specific antigens recognized by T cells that confer protective immunity and ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.00170
更新日期:2020-02-11 00:00:00
abstract::Impairment or stimulation of the immune system by ionizing radiation (IR) impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation an...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00922
更新日期:2018-04-30 00:00:00
abstract::Among kidney transplant recipients, the treatment of choice for acute T cell-mediated rejection (TCMR) with pulse steroids or antibody protocols has variable outcomes. Some rejection episodes are resistant to an initial steroid pulse, but respond to subsequent antibody protocols. The biological mechanisms causing the ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00536
更新日期:2015-11-06 00:00:00
abstract::Monoclonal antibodies against the cell surface antigen CD38, e.g., isatuximab, daratumumab, or Mor202, have entered the therapeutic armamentarium in multiple myeloma due to single agent overall response rates of 29 vs. 36 vs. 31%, effectivity in combination regimen, e.g., with lenalidomide or bortezomib plus dexametha...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.01676
更新日期:2018-07-20 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01842
更新日期:2019-08-06 00:00:00
abstract::In recent years, chimeric antigen receptor (CAR) T-cell therapy has become popular in immunotherapy, particularly after its tremendous success in the treatment of lineage-restricted hematologic cancers. However, the application of CAR T-cell therapy for solid tumors has not reached its full potential because of the la...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01934
更新日期:2017-12-22 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01827
更新日期:2017-12-15 00:00:00
abstract::Dendritic cells (DCs) are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific rol...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00026
更新日期:2012-02-27 00:00:00
abstract::Sialic acids, a group of acidic sugars abundantly expressed in the tissues of deuterostome animals but rarely found in microbes, serve as a "signature of self" for these animals. Cognate sensors for sialic acids include Siglecs, a family of transmembrane lectins of vertebrate immune systems that recognize glycans cont...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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更新日期:2018-12-04 00:00:00
abstract::Susceptibility to ankylosing spondylitis (AS) is polygenic with more than 100 genes identified to date. These include HLA-B27 and the aminopeptidases (ERAP1, ERAP2, and LNPEPS), which are involved in antigen processing and presentation to T-cells, and several genes (IL23R, IL6R, STAT3, JAK2, IL1R1/2, IL12B, and IL7R) ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.03132
更新日期:2019-01-10 00:00:00
abstract::L-selectin (CD62L) is a type-I transmembrane glycoprotein and cell adhesion molecule that is expressed on most circulating leukocytes. Since its identification in 1983, L-selectin has been extensively characterized as a tethering/rolling receptor. There is now mounting evidence in the literature to suggest that L-sele...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01068
更新日期:2019-05-14 00:00:00
abstract::Natural Killer (NK) cells are characterized by their potential to kill tumor cells by different means without previous sensitization and have, therefore, become a valuable tool in cancer immunotherapy. However, their efficacy against solid tumors is still poor and further studies are required to improve it. One of the...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02278
更新日期:2019-09-24 00:00:00
abstract::Dendritic cells (DCs) play a crucial role in initiating and shaping immune responses. The effects of DCs on adaptive immune responses depend partly on functional specialization of distinct DC subsets, and partly on the activation state of DCs, which is largely dictated by environmental signals. Fully activated immunos...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01325
更新日期:2019-06-11 00:00:00
abstract::This article describes the work I did in Bill Paul's lab as a postdoctoral fellow between 1979 and 1983, and to a lesser extent puts that work in the context of other work on B cell activation and antibody responses that was going on in Bill's lab at that time and shortly beforehand, including the discovery of interle...
journal_title:Frontiers in immunology
pub_type: 传,历史文章,杂志文章
doi:10.3389/fimmu.2018.00739
更新日期:2018-04-23 00:00:00