Abstract:
:Myelin basic protein-specific CD8(+) T cells can induce central nervous system autoimmunity; however, immune tolerance prevents these autoreactive cells from causing disease. To define the mechanisms that mediate tolerance, we developed two T cell receptor-transgenic mouse lines with different affinities for the H-2K(k)-restricted myelin basic protein epitope consisting of amino acids 79-87 (MBP(79-87)). We observed both thymic deletion and peripheral tolerance in the lower-affinity T cells. The higher-affinity T cells, however, showed no evidence of tolerance induction and were able to prevent tolerance of the lower-affinity T cells by removing H-2K(k)-MBP(79-87) complexes from antigen-presenting cells without proliferating. This form of immune regulation could limit responses of self-reactive T cells that escape other tolerance mechanisms.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Perchellet A,Stromnes I,Pang JM,Goverman Jdoi
10.1038/ni1073keywords:
subject
Has Abstractpub_date
2004-06-01 00:00:00pages
606-14issue
6eissn
1529-2908issn
1529-2916pii
ni1073journal_volume
5pub_type
杂志文章abstract::The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1-/- mouse B cells, pr...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni907
更新日期:2003-04-01 00:00:00
abstract::CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell act...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni830
更新日期:2002-09-01 00:00:00
abstract::Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1187
更新日期:2005-05-01 00:00:00
abstract::Although master transcription factors (TFs) are key to the development of specific T cell subsets, whether additional transcriptional regulators are induced by the same stimuli that dominantly repress the development of other, non-specific T cell lineages has not been fully elucidated. Through the use of regulatory T ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3667
更新日期:2017-03-01 00:00:00
abstract::The thiol-oxidoreductase ERp57 is an integral component of the peptide-loading complex of the major histocompatibility complex (MHC) class I pathway, but its function is unknown. To investigate its function in antigen presentation, we generated ERp57-deficient mice. Death in utero caused by ubiquitous ERp57 deletion w...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1288
更新日期:2006-01-01 00:00:00
abstract:: ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0147-6
更新日期:2018-07-01 00:00:00
abstract::Membrane recruitment of adaptor proteins is crucial for coupling antigen receptors to downstream signaling events. Despite the essential function of the B cell adaptor SLP-65, the mechanism of its recruitment to the plasma membrane is not yet understood. Here we show that a highly conserved leucine zipper in the SLP-6...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1163
更新日期:2005-02-01 00:00:00
abstract::CD4(+) T cells producing interleukin 17 (IL-17) are associated with autoimmunity, although the precise mechanisms that control their development are undefined. Here we present data that challenge the idea of a shared developmental pathway with T helper type 1 (T(H)1) or T(H)2 lineages and instead favor the idea of a d...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1254
更新日期:2005-11-01 00:00:00
abstract::Induction of the antiviral innate immune response depends on recognition of viral components by host pattern-recognition receptors. Members of the Toll-like receptor family have emerged as key sensors that recognize viral components such as nucleic acids. Toll-like receptor signaling results in the production of type ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1303
更新日期:2006-02-01 00:00:00
abstract::MicroRNAs (miRNAs) exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. We sought to identify miRNAs and miRNA-regulated pathways that control the type 2 helper T cell (TH2 cell) responses that drive pathogenic inflammation in asthma. Profiling miRNA expre...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3026
更新日期:2014-12-01 00:00:00
abstract::Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen-activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was selectively required for lipopolysaccharide-induced activation of p38 but not of Jnk or...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1200
更新日期:2005-06-01 00:00:00
abstract::The extracellular protein Spätzle is required for activation of the Toll signaling pathway in the embryonic development and innate immune defense of Drosophila. Spätzle is synthesized as a pro-protein and is processed to a functional form by a serine protease. We show here that the mature form of Spätzle triggers a To...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni955
更新日期:2003-08-01 00:00:00
abstract::The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a res...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0793-3
更新日期:2020-12-01 00:00:00
abstract::Dendritic cells (DCs) initiate and regulate immunity against foreign and self antigens. Here we identified more than 200 individual major histocompatibility complex class II-associated peptides on human DCs and found that mature DCs selectively upregulated the self peptide CLIP. CLIP cosegregated together with foreign...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1108
更新日期:2004-09-01 00:00:00
abstract::DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1204
更新日期:2005-06-01 00:00:00
abstract::Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8(+) T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intra...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2573
更新日期:2013-06-01 00:00:00
abstract::The immunopathogenesis of rheumatoid arthritis (RA) spans decades, beginning with the production of autoantibodies against post-translationally modified proteins (checkpoint 1). After years of asymptomatic autoimmunity and progressive immune system remodeling, tissue tolerance erodes and joint inflammation ensues as t...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/s41590-020-00816-x
更新日期:2021-01-01 00:00:00
abstract::Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a prote...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0067-5
更新日期:2018-04-01 00:00:00
abstract::Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were m...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3582
更新日期:2016-12-01 00:00:00
abstract::Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Ele...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3385
更新日期:2016-04-01 00:00:00
abstract::NLRX1 is unique among the nucleotide-binding-domain and leucine-rich-repeat (NLR) proteins in its mitochondrial localization and ability to negatively regulate antiviral innate immunity dependent on the adaptors MAVS and STING. However, some studies have suggested a positive regulatory role for NLRX1 in inducing antiv...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3853
更新日期:2017-12-01 00:00:00
abstract::Robert L. Coffman recounts how his work on immunoglobulin E regulation along with data from Tim Mosmann on the functional heterogeneity of T cell clones led to the T helper type 1-T helper type 2 hypothesis. ...
journal_title:Nature immunology
pub_type: 传,历史文章,杂志文章
doi:10.1038/ni0606-539
更新日期:2006-06-01 00:00:00
abstract::Cooperation between different innate signaling pathways induced by pattern-recognition receptors (PRRs) on dendritic cells (DCs) is crucial for tailoring adaptive immunity to pathogens. Here we show that carbohydrate-specific signaling through the C-type lectin DC-SIGN tailored cytokine production in response to disti...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1778
更新日期:2009-10-01 00:00:00
abstract::Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/87766
更新日期:2001-05-01 00:00:00
abstract::Plasma cells are cellular factories devoted entirely to the manufacture and export of a single product: soluble immunoglobulin (Ig). As the final mediators of a humoral response, plasma cells play a critical role in adaptive immunity. Although intense effort has been devoted to studying the regulation and requirements...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1201-1103
更新日期:2001-12-01 00:00:00
abstract::Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in I...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2187
更新日期:2011-11-20 00:00:00
abstract::Emerging concepts suggest that the functional phenotype of macrophages is regulated by transcription factors that define alternative activation states. We found that RBP-J, the main nuclear transducer of signaling via Notch receptors, augmented Toll-like receptor 4 (TLR4)-induced expression of key mediators of classic...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2304
更新日期:2012-05-20 00:00:00
abstract::The importance of protein glycosylation in the migration of immune cells throughout the body has been extensively appreciated. However, our awareness of the impact of glycosylation on the regulation of innate and adaptive immune responses is relatively new. An increasing number of studies reveal the relevance of glyco...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.f.203
更新日期:2008-06-01 00:00:00
abstract::Deletion of the DNA-binding domain of the transcription factor Ikaros generates dominant-negative isoforms that interfere with its activity and correlate with poor prognosis in human precursor B cell acute lymphoblastic leukemia (B-ALL). Here we found that conditional inactivation of the Ikaros DNA-binding domain in e...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2821
更新日期:2014-03-01 00:00:00
abstract::The location of embryonic lymph node development is determined by the initial clustering of lymphoid tissue-inducer (LTi) cells. Here we demonstrate that both the chemokine CXCL13 and the chemokine CCL21 attracted LTi cells at embryonic days 12.5-14.5 and that initial clustering depended exclusively on CXCL13. Retinoi...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1789
更新日期:2009-11-01 00:00:00