Abstract：
:Mycobacterium tuberculosis PtpA, a secreted tyrosine phosphatase essential for tuberculosis pathogenicity, could be an ideal target for a drug against tuberculosis, but its active-site inhibitors lack selectivity over human phosphatases. Here we found that PtpA suppressed innate immunity dependent on pathways of the kinases Jnk and p38 and the transcription factor NF-κB by exploiting host ubiquitin. Binding of PtpA to ubiquitin via a region with no homology to human proteins activated it to dephosphorylate phosphorylated Jnk and p38, leading to suppression of innate immunity. Furthermore, the host adaptor TAB3 mediated NF-κB signaling by sensing ubiquitin chains, and PtpA blocked this process by competitively binding the ubiquitin-interacting domain of TAB3. Our findings reveal how pathogens subvert innate immunity by coopting host ubiquitin and suggest a potential tuberculosis treatment via targeting of ubiquitin-PtpA interfaces.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Wang J,Li BX,Ge PP,Li J,Wang Q,Gao GF,Qiu XB,Liu CHdoi
10.1038/ni.3096subject
Has Abstractpub_date
2015-03-01 00:00:00pages
237-45issue
3eissn
1529-2908issn
1529-2916pii
ni.3096journal_volume
16pub_type
杂志文章abstract：:Innate lymphoid cells (ILCs) are lymphocyte-like cells that lack T cell or B cell antigen receptors and mediate protective and repair functions through cytokine secretion. Among these, type 2 ILCs (ILC2 cells) are able to produce type 2 cytokines. We report the existence of an inflammatory ILC2 (iILC2) population resp...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3078
更新日期：2015-02-01 00:00:00
abstract：:Newly activated CD8(+) T cells reprogram their metabolism to meet the extraordinary biosynthetic demands of clonal expansion; however, the signals that mediate metabolic reprogramming remain poorly defined. Here we demonstrate an essential role for sterol regulatory element-binding proteins (SREBPs) in the acquisition...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2570
更新日期：2013-05-01 00:00:00
abstract：:In recent years, a population of unconventional T cells called 'mucosal-associated invariant T cells' (MAIT cells) has captured the attention of immunologists and clinicians due to their abundance in humans, their involvement in a broad range of infectious and non-infectious diseases and their unusual specificity for ...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/s41590-019-0444-8
更新日期：2019-09-01 00:00:00
abstract：:Tissue-resident macrophages are a heterogeneous population of immune cells that fulfill tissue-specific and niche-specific functions. These range from dedicated homeostatic functions, such as clearance of cellular debris and iron processing, to central roles in tissue immune surveillance, response to infection and the...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.2705
更新日期：2013-10-01 00:00:00
abstract：:EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is as...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/85266
更新日期：2001-03-01 00:00:00
abstract：:Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3229
更新日期：2015-09-01 00:00:00
abstract：:The pre-B cell receptor (preBCR), composed of mu immunoglobulin (Ig) and surrogate light chains, signals large 'preB-II' cells to proliferate in the apparent absence of ligands or cooperating cells. We deleted the N-terminal, nonimmunoglobulin (nonlg) portion of lambda5, or mutated seven arginine residues in it to ser...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni959
更新日期：2003-09-01 00:00:00
abstract：:Actin reorganization at the immunological synapse is required for the amplification and generation of a functional immune response. Using small interfering RNA, we show here that dynamin 2 (Dyn2), a large GTPase involved in receptor-mediated internalization, did not alter antibody-mediated T cell receptor internalizat...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1168
更新日期：2005-03-01 00:00:00
abstract：:Toll-like receptors (TLRs) are key initiators of the innate immune response and promote adaptive immunity. Much has been learned about the role of TLRs in human immunity from studies linking TLR genetic variation with disease. First, monogenic disorders associated with complete deficiency in certain TLR pathways, such...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.2284
更新日期：2012-05-18 00:00:00
abstract：:In the version of this Research Highlight initially published, the url for the linked article was incorrect ( https://doi.org/10.1172/JCI90647JCI90647 ). The correct link is https://doi.org/10.1172/JCI90647 . The error has been corrected in the HTML and PDF versions of the article. ...
journal_title：Nature immunology
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41590-018-0159-2
更新日期：2018-08-01 00:00:00
abstract：:The outcome after infection with the human immunodeficiency virus type 1 (HIV-1) is a complex phenotype determined by interactions among the pathogen, the human host and the surrounding environment. An impact of host genetic variation on HIV-1 susceptibility was identified early in the pandemic, with a major role attr...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.3147
更新日期：2015-06-01 00:00:00
abstract：:CD8+ T cells responding to chronic infections or tumors acquire an 'exhausted' state associated with elevated expression of inhibitory receptors, including PD-1, and impaired cytokine production. Exhausted T cells are continuously replenished by T cells with precursor characteristics that self-renew and depend on the ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-020-0760-z
更新日期：2020-10-01 00:00:00
abstract：:Inflammation is a fundamental protective response that sometimes goes awry and becomes a major cofactor in the pathogenesis of many chronic human diseases, including cancer. Here we review the evolutionary relationship and opposing functions of the transcription factor NF-κB in inflammation and cancer. Although it see...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni.2060
更新日期：2011-07-19 00:00:00
abstract：:All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni1502
更新日期：2007-09-01 00:00:00
abstract：:Fc epsilon RI activation of mast cells is thought to involve Lyn and Syk kinases proximal to the receptor and the signaling complex organized by the linker for activation of T cells (LAT). We report here that Fc epsilon RI also uses a Fyn kinase-dependent pathway that does not require Lyn kinase or the adapter LAT for...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni817
更新日期：2002-08-01 00:00:00
abstract：:Macrophages have protective roles in immunity to pathogens, tissue development, homeostasis and repair following damage. Maladaptive immunity and inflammation provoke changes in macrophage function that are causative of disease. Despite a historical wealth of knowledge about macrophages, recent advances have revealed ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3324
更新日期：2016-01-01 00:00:00
abstract：:The Greek island of Crete became host to lively discussions on immunoregulation as experts from around the world gathered for the 7th Aegean Conference on Autoimmunity in September 2015. ...
journal_title：Nature immunology
pub_type：
doi：10.1038/ni.3367
更新日期：2016-03-01 00:00:00
abstract：:The transcription factor c-Maf induces the anti-inflammatory cytokine IL-10 in CD4+ T cells in vitro. However, the global effects of c-Maf on diverse immune responses in vivo are unknown. Here we found that c-Maf regulated IL-10 production in CD4+ T cells in disease models involving the TH1 subset of helper T cells (m...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-018-0083-5
更新日期：2018-05-01 00:00:00
abstract：:CD8+ T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+ T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue t...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-020-00850-9
更新日期：2021-01-11 00:00:00
abstract：:Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.3564
更新日期：2016-11-01 00:00:00
abstract：:High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/s41590-019-0544-5
更新日期：2019-12-01 00:00:00
abstract：:The transcription factor BATF directly regulates key components of the formation and function of follicular helper T cells and antibody class switching in B cells. ...
journal_title：Nature immunology
pub_type： 评论,新闻
doi：10.1038/ni.2042
更新日期：2011-06-01 00:00:00
abstract：:Plant proteins belonging to the nucleotide-binding site-leucine-rich repeat (NBS-LRR) family are used for pathogen detection. Like the mammalian Nod-LRR protein 'sensors' that detect intracellular conserved pathogen-associated molecular patterns, plant NBS-LRR proteins detect pathogen-associated proteins, most often t...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni1410
更新日期：2006-12-01 00:00:00
abstract：:Susceptibility to complex autoimmune diseases (AIDs) is a multigenic phenotype affected by a variety of genetic and environmental or stochastic factors. After over a decade of linkage analyses, the identification of non-major histocompatibility complex (non-MHC) susceptibility alleles has proved to be difficult, predo...
journal_title：Nature immunology
pub_type： 杂志文章,评审
doi：10.1038/ni0901-802
更新日期：2001-09-01 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：:Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was ...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2622
更新日期：2013-08-01 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：:T cell exhaustion has a major role in failure to control chronic infection. High expression of inhibitory receptors, including PD-1, and the inability to sustain functional T cell responses contribute to exhaustion. However, the transcriptional control of these processes remains unclear. Here we demonstrate that the t...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2046
更新日期：2011-05-29 00:00:00
abstract：:CD11b(+) dendritic cells (DCs) seem to be specialized for presenting antigens via major histocompatibility (MHC) class II complexes to stimulate helper T cells, but the genetic and regulatory basis for this is not established. Conditional deletion of Irf4 resulted in loss of CD11b(+) DCs, impaired formation of peptide...
journal_title：Nature immunology
pub_type： 杂志文章
doi：10.1038/ni.2795
更新日期：2014-02-01 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
