Abstract：
:The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by deubiquitinases that cleave polyubiquitin chains and oppose the function of E3 ubiquitin ligases. Deubiquitinases therefore play an important role in the termination of NF-κB signaling and the resolution of inflammation. In this review, we focus on NF-κB regulation by deubiquitinases with an emphasis on A20 and CYLD. Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Harhaj EW,Dixit VMdoi
10.1111/j.1600-065X.2012.01100.xsubject
Has Abstractpub_date
2012-03-01 00:00:00pages
107-24issue
1eissn
0105-2896issn
1600-065Xjournal_volume
246pub_type
杂志文章,评审abstract：:Rabbits have helped elucidate one of the major immunologic puzzles, namely the genetic control of antibody diversity. The primary IgH antibody repertoire in rabbits is dominated by B cells that use the same germline VH-gene segment in VDJ gene rearrangements. The VDJ genes of essentially all B lymphocytes undergo soma...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01427.x
更新日期：1998-04-01 00:00:00
abstract：:Hematopoietic stem cell transplantation has been used for more than 50 years to combat hematologic malignancies. In addition to being the first stem cell therapy, transplantation has provided evidence for the potent anti-tumor effects of T cells. Facilitating T-cell-based immunity against malignancies requires a caref...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12142
更新日期：2014-01-01 00:00:00
abstract：:The immune system of the gastrointestinal tract must be tightly regulated to limit pathologic responses toward innocuous antigens while simultaneously allowing for rapid development of effector responses against invading pathogens. Highly specialized antigen-presenting cell (APC) subsets present in the gut play a domi...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12167
更新日期：2014-05-01 00:00:00
abstract：:Francisella tularensis in an intracellular bacterial pathogen that causes a potentially lethal disease called tularemia. Studies performed nearly 100 years ago revealed that neutrophil accumulation in infected tissues correlates directly with the extent of necrotic damage during F. tularensis infection. However, the d...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12445
更新日期：2016-09-01 00:00:00
abstract：:Natural killer (NK) cells respond rapidly to transformed, stressed, or virally infected cells and provide a first-line immune defense against pathogen invasion and cancer. Thought to involve short-lived effector cells that are armed for battle, NK cells were not previously known to contribute in recall responses to pa...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2010.00900.x
更新日期：2010-07-01 00:00:00
abstract：:The screening of tumor-derived expression libraries for antigens detected by high-titer immunoglobulin G antibodies from the sera of patients with cancer by SEREX (serological identification of antigens by recombinant expression cloning) allows a systematic search for antigens of human cancers. SEREX has led to the id...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18805.x
更新日期：2002-10-01 00:00:00
abstract：:Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracell...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12266
更新日期：2015-03-01 00:00:00
abstract：:The activation of the complement system by canonical and non-canonical mechanisms results in the generation of multiple C3 and C5 cleavage fragments including anaphylatoxins C3a and C5a as well as opsonizing C3b/iC3b. It is now well appreciated that anaphylatoxins not only act as pro-inflammatory mediators but as immu...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12473
更新日期：2016-11-01 00:00:00
abstract：:Self-tolerance is achieved by deleting or regulating self-reactive lymphocytes at a series of cellular checkpoints placed at many points along the developmental pathways to plasma cells and effector T cells. At each checkpoint, what are the molecular pathways that determine whether a lymphocyte remains quiescent, begi...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2000.00614.x
更新日期：2000-08-01 00:00:00
abstract：:The lung constantly interacts with the environment through thousands of liters of air that are inhaled daily. This continually transports toxic chemicals and particles or pathogenic microorganisms deep into the respiratory system, posing a challenge to physicochemical barriers and the local immune system. Thus, comple...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12020
更新日期：2013-01-01 00:00:00
abstract：:The substantial importance of P-selectin glycoprotein ligand 1 (PSGL-1) in leukocyte trafficking has continued to emerge beyond its initial identification as a selectin ligand. PSGL-1 seemed to be a relatively simple molecule with an extracellular mucin domain extended as a flexible rod, teleologically consistent with...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2009.00797.x
更新日期：2009-07-01 00:00:00
abstract：:Over the past 20 years, major progress has been made in our understanding of natural killer (NK) cells. It has become clear that NK cells are regulated by a number of receptors with opposite functions that finely tune potent effector functions such as cytolytic activity and release of cytokines that play a major role ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00651.x
更新日期：2008-08-01 00:00:00
abstract：:Vaccines or early childhood exposure to infection mediate immunity, that is, improved resistance against disease and death caused by a second infection with the same agent. This has been explained by and equaled to immunological memory, that is, an "altered immune system behavior" that is maintained in a presumably an...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12648
更新日期：2018-05-01 00:00:00
abstract：:The general thrust of this volume is to review the roles of accessory cells in regulating T and B lymphocytes. To that end, we have summarized the evidence that indicates the crucial role that Langerhans cells play in the induction and expression of immunity to antigens that gain access to, or arise within, skin. Lang...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1990.tb00572.x
更新日期：1990-10-01 00:00:00
abstract：:Experiments with transgenic mice illustrate clonal elimination of T cells specific for antigens expressed appropriately in the thymus, but presence of inducible T cells when the antigen presented on class I MHC antigens is expressed exclusively on non-lymphohemopoietic cells in the periphery (pancreatic beta islet cel...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1991.tb00601.x
更新日期：1991-08-01 00:00:00
abstract：:Highlights in a 4-decade exploration of lymphocyte differentiation begin with comparative studies in birds and mammals leading to recognition of the separate T- and B-cell differentiation pathways and their cooperative interaction. The global effects of aborting IgM B-cell development with anti-mu antibodies indicated...
journal_title：Immunological reviews
pub_type： 历史文章,杂志文章,评审
doi：10.1034/j.1600-065x.2002.18515.x
更新日期：2002-07-01 00:00:00
abstract：:Cancers are able to grow by subverting immune suppressive pathways, to prevent the malignant cells as being recognized as dangerous or foreign. This mechanism prevents the cancer from being eliminated by the immune system and allows disease to progress from a very early stage to a lethal state. Immunotherapies are new...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12528
更新日期：2017-03-01 00:00:00
abstract：:The individual role of pathogen-binding Toll-like receptors (TLRs) and antibody-binding Fc receptors (FcRs) during pathogenic infections has been studied extensively. However, combined activation of these different receptor classes has received little attention, even though they are triggered simultaneously when immun...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12333
更新日期：2015-11-01 00:00:00
abstract：:The processes of T-cell development and activation employ similar immature and mature receptors as well as similar signal transduction pathways to achieve different outcomes. Many signaling molecules are shared between the receptor signaling pathways, including two families of cytoplasmic protein tyrosine kinases, the...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1998.tb01238.x
更新日期：1998-10-01 00:00:00
abstract：:Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter of the spinal cord with chronic inflammation and demyelination. This late disease is studied as a model for multiple sclerosis. Inbred strains of mice differ in their susceptibility...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1997.tb01014.x
更新日期：1997-10-01 00:00:00
abstract：:In the century since Paul Portier and Charles Richet described their landmark findings of severe fatal reactions in dogs re-exposed to venom after vaccination with sea anemone venom, treatment for anaphylaxis continues to evolve. The incidence of anaphylaxis continues to be difficult to measure. Underreporting due to ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2011.01028.x
更新日期：2011-07-01 00:00:00
abstract：:Studies in the last 20 years have given us a remarkable insight into the functional and phenotypic diversity of macrophages which reflects their integral role in host defence, homeostasis and pathogenesis. Mouse genetics, transcriptomic and epigenetic studies have provided an ontogenic and molecular perspective to the...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12603
更新日期：2017-11-01 00:00:00
abstract：:The development of vaccines is presently receiving major attention in malaria research. As it is not possible to base malaria vaccines on the use of killed or attenuated organisms, the vaccines which are being developed are subunit vaccines in which the immunogens consist of defined parasite antigens or antigenic frag...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065x.1989.tb00555.x
更新日期：1989-12-01 00:00:00
abstract：:Expressed predominantly on myeloid and natural killer (NK) cells, DAP12 is an adapter protein that can associate with a variety of receptors. To date, DAP12 has predominantly been characterized as an adapter protein that activates various myeloid and NK cell effector functions; however, recent findings have demonstrat...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2006.00466.x
更新日期：2006-12-01 00:00:00
abstract：:The immune system is capable of recognizing and eliminating an enormous array of pathogens due to the extremely diverse antigen receptor repertoire of T and B lymphocytes. However, the development of lymphocytes bearing receptors with unique specificities requires the generation of programmed double strand breaks (DSB...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2006.00361.x
更新日期：2006-02-01 00:00:00
abstract：:Fcγ receptors (FcγRs) are key immune receptors responsible for the effective control of both humoral and innate immunity and are central to maintaining the balance between generating appropriate responses to infection and preventing autoimmunity. When this balance is lost, pathology results in increased susceptibility...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/imr.12341
更新日期：2015-11-01 00:00:00
abstract：:Solid tumor therapy with chemotherapeutics greatly depends on the efficiency with which drugs are delivered to tumor cells. The typical characteristics of the tumor physiology promote but also appose accumulation of blood-borne agents. The leaky tumor vasculature allows easy passage of drugs. However, the disorganized...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.1600-065X.2008.00619.x
更新日期：2008-04-01 00:00:00
abstract：:The cellular and molecular mechanisms underlying the formation of distinct central, effector, and exhausted CD8+ T-cell memory subsets were first described in the setting of acute and chronic viral diseases. The role of these T-cell memory subsets are now being illuminated as relevant to the tumor-bearing state. The g...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2006.00391.x
更新日期：2006-06-01 00:00:00
abstract：:Understanding how the integrins on leukocytes operate is important because these receptors control the activity of leukocytes in all phases of their lives. Thus integrins control leukocyte development and maturation in bone marrow, the circulation of naive cells in secondary lymphoid tissue, e.g. the lymph nodes, and ...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1034/j.1600-065x.2002.18614.x
更新日期：2002-08-01 00:00:00
abstract：:Schistosomiasis is a serious global helminthic disease, in which the main immunopathology consists of a granulomatous and fibrosing reaction against tissue-trapped parasite eggs. The severity of this inflammatory process, the product of a CD4(+) T-cell-mediated immune response against parasite egg antigens, is, howeve...
journal_title：Immunological reviews
pub_type： 杂志文章,评审
doi：10.1111/j.0105-2896.2004.00197.x
更新日期：2004-10-01 00:00:00
