Abstract:
:Toll-like receptor-4 activation by lipopolysaccharide (LPS) induces the expression of interferon-beta (IFN-beta) in a MyD88-independent manner. Here we report that mice devoid of the JAK protein tyrosine kinase family member, Tyk2, were resistant to shock induced by high doses of LPS. Basal and LPS-induced expression of IFN-beta and IFN-alpha4 mRNA in Tyk2-null macrophages were diminished. However, Tyk2-null mice showed normal systemic production of nitric oxide and proinflammatory cytokines and the in vivo response to tumor necrosis factor (TNF) was unperturbed. IFN-beta-null but not STAT1-null mice were also resistant to high dose LPS treatment. Together, these data suggest that Tyk2 and IFN-beta are essential effectors in LPS induced lethality.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Karaghiosoff M,Steinborn R,Kovarik P,Kriegshäuser G,Baccarini M,Donabauer B,Reichart U,Kolbe T,Bogdan C,Leanderson T,Levy D,Decker T,Müller Mdoi
10.1038/ni910keywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
471-7issue
5eissn
1529-2908issn
1529-2916pii
ni910journal_volume
4pub_type
杂志文章abstract::Despite their central function in orchestrating immunity, dendritic cells (DCs) can respond to inhibitory signals by becoming tolerogenic. Here we show that galectin-1, an endogenous glycan-binding protein, can endow DCs with tolerogenic potential. After exposure to galectin-1, DCs acquired an interleukin 27 (IL-27)-d...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1772
更新日期:2009-09-01 00:00:00
abstract::Myxoma virus, a member of the poxvirus family, causes lethal infection only in rabbits, but the mechanism underlying the strict myxoma virus species barrier is not known. Here we show that myxoma virus infection of primary mouse embryo fibroblasts elicited extracellular signal-regulated kinase (Erk) signaling, which w...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1132
更新日期:2004-12-01 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::T lymphocytes and B lymphocytes integrate activating signals to control the size of their proliferative response. Here we report that such control was achieved by timed changes in the production rate of cell-cycle-regulating proto-oncoprotein Myc, with division cessation occurring when Myc levels fell below a critical...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3598
更新日期:2017-01-01 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::Caspases are important for apoptosis but are also involved in mammalian cell survival and cell division. Here we report that caspase-3 is a negative regulator of B cell cycling. Mice deficient in caspase-3 (Casp3-/- mice) have increased numbers of splenic B cells that show normal apoptosis but enhanced proliferation i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni976
更新日期:2003-10-01 00:00:00
abstract::Plasticity is a hallmark of cells of the myelomonocytic lineage. In response to innate recognition or signals from lymphocyte subsets, mononuclear phagocytes undergo adaptive responses. Shaping of monocyte-macrophage function is an essential component of resistance to pathogens, tissue damage and repair. The orchestra...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.1937
更新日期:2010-10-01 00:00:00
abstract::Interactions driven by the T cell antigen receptor (TCR) determine the lineage fate of CD4(+)CD8(+) thymocytes, but the molecular mechanisms that induce the lineage-determining transcription factors are unknown. Here we found that TCR-induced transcription factors Egr2 and Egr1 had higher and more-prolonged expression...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2230
更新日期:2012-02-05 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::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::The mechanisms that initiate T helper type 2 (T(H)2) responses are poorly understood. Here we demonstrate that cysteine protease-induced T(H)2 responses occur via 'cooperation' between migratory dermal dendritic cells (DCs) and basophils positive for interleukin 4 (IL-4). Subcutaneous immunization with papain plus ant...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1883
更新日期:2010-07-01 00:00:00
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 ess...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3632
更新日期:2017-01-01 00:00:00
abstract::Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3200
更新日期:2015-07-01 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::The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechani...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2820
更新日期:2014-03-01 00:00:00
abstract::Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, g...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1935
更新日期:2010-10-01 00:00:00
abstract::Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional amo...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0598-4
更新日期:2020-03-01 00:00:00
abstract::The transcription factor c-Myb is expressed throughout T cell development in the thymus. However, little is understood about c-Myb function because of the embryonic lethality of traditional Myb-null mutations. Using tissue-specific deletion to abrogate c-Myb expression at distinct stages of T cell development, we iden...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1085
更新日期:2004-07-01 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::Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell a...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2928
更新日期:2014-08-01 00:00:00
abstract::Using whole-genome microarray data sets of the Immunological Genome Project, we demonstrate a closer transcriptional relationship between NK cells and T cells than between any other leukocytes, distinguished by their shared expression of genes encoding molecules with similar signaling functions. Whereas resting NK cel...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2395
更新日期:2012-10-01 00:00:00
abstract::The relationship between the T cell receptor (TCR) repertoires used by self-reactive transcription factor Foxp3-positive (Foxp3(+)) CD4(+) regulatory T cells (T(reg) cells) and nonregulatory T cells with autoimmune potential is unclear. Here we found that the TCR repertoire of thymic T(reg) cells in TCRbeta-transgenic...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1318
更新日期:2006-04-01 00:00:00
abstract::Innate T cells, including invariant natural killer T (iNKT) and mucosal-associated innate T (MAIT) cells, are a heterogeneous T lymphocyte population with effector properties preprogrammed during their thymic differentiation. How this program is initiated is currently unclear. Here, we show that the transcription fact...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0737-y
更新日期:2020-09-01 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::Nedd4 and Itch are E3 ubiquitin ligases that ubiquitinate similar targets in vitro and thus are thought to function similarly. T cells lacking Itch show spontaneous activation and T helper type 2 polarization. To test whether loss of Nedd4 affects T cells in the same way, we generated Nedd4(+/+) and Nedd4(-/-) fetal l...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.1670
更新日期:2008-12-01 00:00:00
abstract::High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, b...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2022
更新日期:2011-05-01 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::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature immunology
pub_type: 已发布勘误
doi:10.1038/s41590-019-0545-4
更新日期:2019-12-01 00:00:00
abstract::The ubiquitin-editing enzyme A20 is a critical negative regulator of inflammation and cytokine-mediated activation of the transcription factor NF-kappaB; however, little is known about the mechanisms of A20-mediated inactivation of signaling intermediates such as RIP1. Here we demonstrate that the regulatory molecule ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1563
更新日期:2008-03-01 00:00:00
abstract::Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'i...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1239
更新日期:2005-09-01 00:00:00