Abstract：
:The cause of common polygenic autoimmune diseases is not understood because of genetic and cellular complexity. Here, we pinpoint the action of a subset of autoimmune susceptibility loci in the NOD mouse strain linked to D1mit181, D2mit490, D7mit101, and D15mit229, which cause a generalized resistance to thymic deletion in vivo that applies equally to Aire-induced organ-specific gene products in the thymic medulla and to systemic antigens expressed at high levels throughout the thymus and affects CD4(+), CD4(+)8(+), and CD4(+)25(+) thymocytes. Resistance to thymic deletion does not reflect a general deficit in TCR signaling to calcineurin- or ERK-induced genes, imbalance in constitutive regulators of apoptosis, nor excessive signaling to prosurvival genes but is distinguished by failure to induce the proapoptotic gene and protein, Bim, during in vivo encounter with high-avidity autoantigen. These findings establish defects in thymic deletion and Bim induction as a key mechanism in the pathogenesis of autoimmunity.
journal_name
Immunityjournal_title
Immunityauthors
Liston A,Lesage S,Gray DH,O'Reilly LA,Strasser A,Fahrer AM,Boyd RL,Wilson J,Baxter AG,Gallo EM,Crabtree GR,Peng K,Wilson SR,Goodnow CCdoi
10.1016/j.immuni.2004.10.014keywords:
subject
Has Abstractpub_date
2004-12-01 00:00:00pages
817-30issue
6eissn
1074-7613issn
1097-4180pii
S1074-7613(04)00313-9journal_volume
21pub_type
杂志文章相关文献
IMMUNITY文献大全abstract：:How antigen valency affects B cells in vivo during immune responses is not well understood. Here, using HIV immunogens with defined valencies ranging from 1 to 60, we investigated the role of antigen valency during different phases of B cell responses in vivo. Highly multimerized immunogens preferentially rapidly acti...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2020.08.001
更新日期：2020-09-15 00:00:00
abstract：:Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2011.06.009
更新日期：2011-08-26 00:00:00
abstract：:Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immu...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2017.02.011
更新日期：2017-03-21 00:00:00
abstract：:To explain why solid cancers grow or are rejected, we examined how the tumor stroma affected the level of antigen expression necessary to induce an immune response. We applied a tamoxifen-regulated Cre-loxP system to induce a model SIYRYYGL antigen recognized by the 2C T cell receptor. Solid tumors expressing the anti...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(02)00480-6
更新日期：2002-12-01 00:00:00
abstract：:Immunoglobulin G (IgG) antibodies confer protection against pathogenic microorganisms, serve as therapeutics in tumor therapy, and are involved in destruction of healthy tissues during autoimmune diseases. Understanding the molecular pathways and effector cell types involved in antibody-mediated effector functions is ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2011.11.009
更新日期：2011-12-23 00:00:00
abstract：:Fever, an evolutionarily conserved physiological response to infection, is also commonly associated with many autoimmune diseases, but its role in T cell differentiation and autoimmunity remains largely unclear. T helper 17 (Th17) cells are critical in host defense and autoinflammatory diseases, with distinct phenotyp...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2020.01.006
更新日期：2020-02-18 00:00:00
abstract：:To establish whether the widely expressed regulator of Src family kinases Csk contributes to the control of acute inflammation in vivo, we inactivated csk in granulocytes by conditional mutagenesis (Cre/loxP). Mutant mice (Csk-GEcre) developed acute multifocal inflammation in skin and lung. Animals were protected from...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(04)00023-8
更新日期：2004-02-01 00:00:00
abstract：:The regulation of actin dynamics is pivotal for cellular processes such as cell adhesion, migration, and phagocytosis and thus is crucial for neutrophils to fulfill their roles in innate immunity. Many factors have been implicated in signal-induced actin polymerization, but the essential nature of the potential negati...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2012.08.017
更新日期：2012-12-14 00:00:00
abstract：:For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL) clones exhibit a decrease in their effector activity and in their binding to human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8. Effecto...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2008.01.011
更新日期：2008-03-01 00:00:00
abstract：:A key event in the pathogenesis of asthma and allergies is the production of IgE antibodies. We show here that IgE(+) cells were exceptional because they were largely found outside germinal centers and expressed, from very early on, a genetic program of plasma cells. In spite of their extragerminal center localization...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2006.12.006
更新日期：2007-02-01 00:00:00
abstract：:B7-0 or B7-2 (CD86) is a T cell costimulatory molecule that binds the same receptors (CD28 and CTLA-4) as B7-1 (CD80), but shares with it only approximately 25% sequence identity and is expressed earlier during an immune response. Here we show that human CD86 maintains similar (within approximately 2- to 3-fold) overa...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(94)80021-9
更新日期：1994-12-01 00:00:00
abstract：:Inflammasomes are supramolecular organizing centers that operate to drive interleukin-1 (IL-1)-dependent inflammation. Depending on context, inflammatory caspases act upstream or downstream of inflammasome assembly, serving as the principal enzymes that control activities of these organelles. In this review, we discus...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2019.08.005
更新日期：2019-10-15 00:00:00
abstract：:Murine natural killer cells selectively express members of the Ly49 family of class I MHC receptors; however, the molecular mechanism controlling probabilistic expression of Ly49 proteins has not been defined. A pair of overlapping, divergent promoters discovered in the Ly49g gene functions as a molecular switch that ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2004.06.005
更新日期：2004-07-01 00:00:00
abstract：:Blood, lymphoid tissues, and placenta contain diverse subpopulations of natural killer (NK) cells that possess distinct immune functions. Recent studies have shown that human and mouse gut-associated lymphoid tissues harbor a unique NK cell subset that specializes in production of interleukin (IL)-22. This cytokine pl...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2009.06.008
更新日期：2009-07-17 00:00:00
abstract：:The transcription factor Blimp-1 regulates the overall accumulation of virus-specific CD8⁺ T cells during acute viral infections. We found that increased proliferation and survival of Blimp-1-deficient CD8⁺ T cells resulted from sustained expression of CD25 and CD27 and persistent cytokine responsiveness. Silencing of...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2013.08.032
更新日期：2013-10-17 00:00:00
abstract：:The central nervous system undergoes extensive postnatal synapse remodeling that is critical for the formation of mature neural circuits. In a recent issue of Science, Vainchtein et al. (2018) describe an additional role for astrocyte-derived interleukin-33 (IL-33) in promoting synapse refinement by microglia in the d...
journal_title：Immunity
pub_type： 信件
doi：10.1016/j.immuni.2018.03.005
更新日期：2018-03-20 00:00:00
abstract：:Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a sing...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2016.04.014
更新日期：2016-05-17 00:00:00
abstract：:Two recent Immunity papers link peripheral tolerance with the ability of developing B cells to capture BAFF. These findings suggest that an increase in effective BAFF levels leads to autoreactive B cell maturation. ...
journal_title：Immunity
pub_type： 评论,杂志文章
doi：10.1016/j.immuni.2004.06.001
更新日期：2004-06-01 00:00:00
abstract：:Apoptosis in response to granzyme B involves activation of caspase-dependent target cell death pathways. Herein, we show that granzyme B initiates caspase processing but cannot fully process procaspase-3 in intact Jurkat T leukemia or NT2 neuronal cells. Rather, the release from mitochondria of proapoptotic mediators ...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/s1074-7613(03)00050-5
更新日期：2003-03-01 00:00:00
abstract：:Antigen-presenting cells (APC) degrade proteins intracellularly to generate peptides, which are then bound by products of the major histocompatibility complex (MHC) and exposed on the surface of the APC for recognition by T cells. The supply of antigenic peptides and their association with MHC molecules requires the c...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/s1074-7613(00)80176-4
更新日期：2000-03-01 00:00:00
abstract：:The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagene...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2005.01.018
更新日期：2005-04-01 00:00:00
abstract：:Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system, receptor protein tyro...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2015.07.009
更新日期：2015-08-18 00:00:00
abstract：:Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and e...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2017.10.015
更新日期：2017-11-21 00:00:00
abstract：:Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the infla...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2017.06.008
更新日期：2017-06-20 00:00:00
abstract：:Toll-like receptors (TLRs) are the archetypal pattern recognition receptors (PRRs) envisioned by as innate sensors of pathogen attack and host triggers of an adaptive immune response. Two recent papers (Choe et al., 2005; Bell et al., 2005) reveal the distinctive architecture of a TLR sensor domain and hint at how thi...
journal_title：Immunity
pub_type： 杂志文章,评审
doi：10.1016/j.immuni.2005.09.008
更新日期：2005-10-01 00:00:00
abstract：:Reprogramming of cellular metabolism is crucial for T cells responding to environmental cues. Blagih et al. (2015) reveal that the kinase AMPK directs metabolic adaption of effector T cells upon nutrient limitation and contributes to immune responses in vivo. ...
journal_title：Immunity
pub_type： 评论,杂志文章
doi：10.1016/j.immuni.2014.12.029
更新日期：2015-01-20 00:00:00
abstract：:CD70 and CD27 are costimulatory molecules that provide essential signals for the expansion and differentiation of CD8(+) T cells. Here, we show that CD27-driven costimulation lowered the threshold of T cell receptor activation on CD8(+) T cells and enabled responses against low-affinity antigens. Using influenza infec...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2011.04.020
更新日期：2011-07-22 00:00:00
abstract：:Activation of the RIG-I signaling molecule is essential for antiviral immunity but mechanisms downmodulating the response are ill defined. In this issue of Immunity, Rajput et al. (2011) describe caspase-8-mediated RIP1 cleavage as a key step for restricting RIG-I signaling. ...
journal_title：Immunity
pub_type： 评论,杂志文章
doi：10.1016/j.immuni.2011.03.011
更新日期：2011-03-25 00:00:00
abstract：:Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor cell death and trans...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2015.03.009
更新日期：2015-04-21 00:00:00
abstract：:Multipotential naive CD4(+) T cells differentiate into distinct lineages including T helper 1 (Th1), Th2, Th17, and inducible T regulatory (iTreg) cells. The remarkable diversity of CD4(+) T cells begs the question whether the observed changes reflect terminal differentiation with heritable epigenetic modifications or...
journal_title：Immunity
pub_type： 杂志文章
doi：10.1016/j.immuni.2008.12.009
更新日期：2009-01-16 00:00:00
