Abstract:
:Feedback regulatory circuits provided by regulatory T cells (T(reg) cells) and suppressive cytokines are an intrinsic part of the immune system, along with effector functions. Here we discuss some of the regulatory cytokines that have evolved to permit tolerance to components of self as well as the eradication of pathogens with minimal collateral damage to the host. Interleukin 2 (IL-2), IL-10 and transforming growth factor-β (TGF-β) are well characterized, whereas IL-27, IL-35 and IL-37 represent newcomers to the spectrum of anti-inflammatory cytokines. We also emphasize how information accumulated through in vitro as well as in vivo studies of genetically engineered mice can help in the understanding and treatment of human diseases.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Banchereau J,Pascual V,O'Garra Adoi
10.1038/ni.2406subject
Has Abstractpub_date
2012-10-01 00:00:00pages
925-31issue
10eissn
1529-2908issn
1529-2916pii
ni.2406journal_volume
13pub_type
杂志文章,评审abstract::Regenerative stem cell-like memory (TSCM) CD8+ T cells persist longer and produce stronger effector functions. We found that MEK1/2 inhibition (MEKi) induces TSCM that have naive phenotype with self-renewability, enhanced multipotency and proliferative capacity. This is achieved by delaying cell division and enhancing...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-00818-9
更新日期:2021-01-01 00:00:00
abstract::In addition to the conventional innate and acquired immune responses, complex organisms have evolved an array of dominant, constitutively expressed genes that suppress or prevent viral infections. Two major cellular defenses against infection by retroviruses are the Fv1 and TRIM5 class of inhibitors that target incomi...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1125
更新日期:2004-11-01 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::The ST2L receptor for interleukin 33 (IL-33) mediates pulmonary inflammation and immune system-related disorders, such as asthma and rheumatoid arthritis. At present, very little is known about the molecular regulation of ST2L expression. Here we found that FBXL19, an 'orphan' member of the Skp1-Cullin-F-box family of...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2341
更新日期:2012-06-03 00:00:00
abstract::The activation of an immune response requires recognition of microorganisms by host receptors. In drosophila, detection of Gram-positive bacteria is mediated by cooperation between the peptidoglycan-recognition protein-SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1) proteins. Here we show that some Gram-posit...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1123
更新日期:2004-11-01 00:00:00
abstract::Mechanisms that degrade inflammatory mRNAs are well known; however, stabilizing mechanisms are poorly understood. Here, we show that Act1, an interleukin-17 (IL-17)-receptor-complex adaptor, binds and stabilizes mRNAs encoding key inflammatory proteins. The Act1 SEFIR domain binds a stem-loop structure, the SEFIR-bind...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0071-9
更新日期:2018-04-01 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::The family of mammalian Nod-like receptors (NLRs) consists of critical intracellular immune proteins structurally related to plant resistance proteins. The NLRs NALP3 and IPAF, for example, can each form a multiprotein proinflammatory complex called the 'inflammasome', and mutations in the gene encoding Nod2, another ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1459
更新日期:2007-05-01 00:00:00
abstract::Invariant natural killer T cells (iNKT cells) are innate-like T lymphocytes that act as critical regulators of the immune response. To better characterize this population, we profiled gene expression in iNKT cells during ontogeny and in peripheral subsets as part of the Immunological Genome Project. High-resolution co...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2490
更新日期:2013-01-01 00:00:00
abstract::Diverse cellular responses to external cues are controlled by a small number of signal-transduction pathways, but how the specificity of functional outcomes is achieved remains unclear. Here we describe a mechanism for signal integration based on the functional coupling of two distinct signaling pathways widely used i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2845
更新日期:2014-04-01 00:00:00
abstract::We evaluated changes in the signaling potentials and proliferative capacity of single antigen-specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/80841
更新日期:2000-11-01 00:00:00
abstract::Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during ly...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1695
更新日期:2009-02-01 00:00:00
abstract::Vaccines against important enteric pathogens such as rotavirus and poliovirus have shown lower efficacy in some populations. The application of new technologies and diverse scientific disciplines are needed to realize the promise of truly universal and effective solutions to combat those and other enteric diseases. ...
journal_title:Nature immunology
pub_type:
doi:10.1038/ni0910-769
更新日期:2010-09-01 00:00:00
abstract::The immune response is orchestrated by a variety of immune cells. The function of each cell is determined by the collective signals from various immunoreceptors, whose expression and activity depend on the developmental stages of the cell and its environmental context. Recent studies have highlighted the presence of m...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0491-1
更新日期:2019-10-01 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
abstract::Post-translational modification of chemokines mediated by the dipeptidyl peptidase DPP4 (CD26) has been shown to negatively regulate lymphocyte trafficking, and its inhibition enhances T cell migration and tumor immunity by preserving functional chemokine CXCL10. By extending those initial findings to pre-clinical mod...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0321-5
更新日期:2019-03-01 00:00:00
abstract::Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome-independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1862
更新日期:2010-05-01 00:00:00
abstract::T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappaB components NF-kappaB1-RelA. The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects....
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1351
更新日期:2006-07-01 00:00:00
abstract::Plasma cell differentiation requires silencing of B cell transcription, while it establishes antibody-secretory function and long-term survival. The transcription factors Blimp-1 and IRF4 are essential for the generation of plasma cells; however, their function in mature plasma cells has remained elusive. We found tha...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3348
更新日期:2016-03-01 00:00:00
abstract::Endoplasmic reticulum (ER) aminopeptidase 1 (ERAP1) appears to be specialized to produce peptides presented on class I major histocompatibility complex molecules. We found that purified ERAP1 trimmed peptides that were ten residues or longer, but spared eight-residue peptides. In vivo, ERAP1 enhanced production of an ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni860
更新日期:2002-12-01 00:00:00
abstract::Innate lymphoid cells (ILCs) are tissue-resident sentinels that are essential for early host protection from pathogens at initial sites of infection. However, whether pathogen-derived antigens directly modulate the responses of tissue-resident ILCs has remained unclear. In the present study, it was found that liver-re...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0430-1
更新日期:2019-08-01 00:00:00
abstract::We define here the specificity and significance of proteases in the endoplasmic reticulum (ER) that generate peptides for presentation by major histocompatibility complex (MHC) class I molecules. We show that aminopeptidases efficiently trimmed all residues except proline that flank the NH2-termini of antigenic precur...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/89800
更新日期:2001-07-01 00:00:00
abstract::The lineage commitment of CD4+ T cells is coordinately regulated by signals through the T cell receptor and cytokine receptors, yet how these signals are integrated remains elusive. Here we find that mice lacking Dock2, a Rac activator in lymphocytes, developed allergic disease through a mechanism dependent on CD4+ T ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1506
更新日期:2007-10-01 00:00:00
abstract::Recent studies have highlighted the structural requirements for T cell costimulation and have revealed unusual modes of dimerization for the cytolytic T lymphocyte-associated antigen 4 (CTLA-4) costimulatory receptor and its B7 ligands. These distinctive quaternary structures potentially endow both receptor and ligand...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni0502-427
更新日期:2002-05-01 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::Invariant natural killer T cells (iNKT cells) are innate-like lymphocytes that protect against infection, autoimmune disease and cancer. However, little is known about the epigenetic regulation of iNKT cell development. Here we found that the H3K27me3 histone demethylase UTX was an essential cell-intrinsic factor that...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3644
更新日期:2017-02-01 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::Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-transl...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3487
更新日期:2016-08-01 00:00:00
abstract::CD1 proteins present various glycolipid antigens to T cells, but the cellular mechanisms that control which particular glycolipids generate T cell responses are not understood. We show here that T cell recognition of glucose monomycolate antigens with long (C(80)) alkyl chains involves the delivery of CD1b proteins an...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni780
更新日期:2002-05-01 00:00:00
abstract::T cell antigen receptor (TCR) signaling drives distinct responses depending on the differentiation state and context of CD8(+) T cells. We hypothesized that access of signal-dependent transcription factors (TFs) to enhancers is dynamically regulated to shape transcriptional responses to TCR signaling. We found that th...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3441
更新日期:2016-07-01 00:00:00