Abstract:
:The cellular sources of interleukin 6 (IL-6) that are relevant for differentiation of the TH17 subset of helper T cells remain unclear. Here we used a novel strategy for the conditional deletion of distinct IL-6-producing cell types to show that dendritic cells (DCs) positive for the signaling regulator Sirpα were essential for the generation of pathogenic TH17 cells. Using their IL-6 receptor α-chain (IL-6Rα), Sirpα+ DCs trans-presented IL-6 to T cells during the process of cognate interaction. While ambient IL-6 was sufficient to suppress the induction of expression of the transcription factor Foxp3 in T cells, trans-presentation of IL-6 by DC-bound IL-6Rα (called 'IL-6 cluster signaling' here) was needed to prevent premature induction of interferon-γ (IFN-γ) expression in T cells and to generate pathogenic TH17 cells in vivo. Our findings should guide therapeutic approaches for the treatment of TH17-cell-mediated autoimmune diseases.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Heink S,Yogev N,Garbers C,Herwerth M,Aly L,Gasperi C,Husterer V,Croxford AL,Möller-Hackbarth K,Bartsch HS,Sotlar K,Krebs S,Regen T,Blum H,Hemmer B,Misgeld T,Wunderlich TF,Hidalgo J,Oukka M,Rose-John S,Schmidt-Suppdoi
10.1038/ni.3632subject
Has Abstractpub_date
2017-01-01 00:00:00pages
74-85issue
1eissn
1529-2908issn
1529-2916pii
ni.3632journal_volume
18pub_type
杂志文章abstract::The survival of T lymphocytes requires sustained, Ca(2+) influx-dependent gene expression. The molecular mechanism that governs sustained Ca(2+) influx in naive T lymphocytes is unknown. Here we report an essential role for the beta3 regulatory subunit of voltage-gated calcium (Ca(v)) channels in the maintenance of na...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1793
更新日期:2009-12-01 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::Autophagy is an intracellular bulk degradation system that is highly conserved in eukaryotes. The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes. In add...
journal_title:Nature immunology
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doi:10.1038/ni.3273
更新日期:2015-10-01 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::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(...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1073
更新日期:2004-06-01 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::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::Interleukin 17 (IL-17)-producing T helper 17 cells (T(H)-17 cells) have been described as a T helper cell subset distinct from T helper type 1 (T(H)1) and T(H)2 cells, with specific functions in antimicrobial defense and autoimmunity. The factors driving human T(H)-17 differentiation remain controversial. Using a syst...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1613
更新日期:2008-06-01 00:00:00
abstract::As part of the most important contributions to the understanding of viral immunity, Michael Oldstone recounts his pioneering work on lymphocytic choriomeningitis virus. ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni0407-325
更新日期:2007-04-01 00:00:00
abstract::Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is act...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1028
更新日期:2004-02-01 00:00:00
abstract::Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adapto...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2888
更新日期:2014-06-01 00:00:00
abstract::After homing to lymph nodes, CD8+ T cells are primed by dendritic cells (DCs) in three phases. During phase one, T cells undergo brief serial contacts with DCs for several hours, whereas phase two is characterized by stable T cell-DC interactions. We show here that the duration of phase one and T cell activation kinet...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1559
更新日期:2008-03-01 00:00:00
abstract::Oxidants such as H2O2 are connected to lymphocyte activation, but the molecular mechanisms behind this phenomenon are less clear. Here, I review data suggesting that by inhibiting protein tyrosine phosphatases, H2O2 plays an important role as a secondary messenger in the initiation and amplification of signaling at th...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1202-1129
更新日期:2002-12-01 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::Cytomegalovirus (CMV), measles and HIV are the main human pathogens known to induce immunosuppression. Unlike measles and HIV, and despite the availability of a well studied animal model, little is known about the mechanisms that control CMV-induced immunosuppression. We hypothesized that dendritic cells (DCs), which ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni724
更新日期:2001-11-01 00:00:00
abstract::Interferon-γ (IFN-γ) is essential for the innate immune response to intracellular bacteria. Noncoding RNAs and RNA-binding proteins (RBPs) need to be further considered in studies of regulation of the IFN-γ-activated signaling pathway in macrophages. In the present study, we found that the microRNA miR-1 promoted IFN-...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0542-7
更新日期:2019-12-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1458
更新日期:2007-05-01 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
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2961
更新日期:2014-10-01 00:00:00
abstract::The signaling pathways that regulate B and T lymphocytes are remarkably conserved between humans and mice. However, recent evidence suggests that the pathways regulating natural killer (NK) cell activation may actually differ between these two species. We discuss the controversies in the field and propose that this di...
journal_title:Nature immunology
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更新日期:2002-09-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1288
更新日期:2006-01-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1475
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更新日期:2007-01-01 00:00:00
abstract:: ...
journal_title:Nature immunology
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更新日期:2018-11-01 00:00:00
abstract::Store-operated Ca2+ entry through calcium release-activated calcium channels is the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium sen...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1574
更新日期:2008-04-01 00:00:00
abstract::The glycolipid alpha-galactosylceramide binds with high affinity to CD1d and stimulates natural killer T cells. Here we report the crystal structure of human CD1d in complex with synthetic alpha-galactosylceramide at a resolution of 3.0 A. The structure shows a tightly fit lipid in the CD1d binding groove, with the sp...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1225
更新日期:2005-08-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/83183
更新日期:2001-01-01 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::Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcrip...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3257
更新日期:2015-10-01 00:00:00
abstract::A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations ...
journal_title:Nature immunology
pub_type: 杂志文章
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