Abstract:
:The origin and specification of human dendritic cells (DCs) have not been investigated at the clonal level. Through the use of clonal assays, combined with statistical computation, to quantify the yield of granulocytes, monocytes, lymphocytes and three subsets of DCs from single human CD34+ progenitor cells, we found that specification to the DC lineage occurred in parallel with specification of hematopoietic stem cells (HSCs) to the myeloid and lymphoid lineages. This started as a lineage bias defined by specific transcriptional programs that correlated with the combinatorial 'dose' of the transcription factors IRF8 and PU.1, which was transmitted to most progeny cells and was reinforced by upregulation of IRF8 expression driven by the hematopoietic cytokine FLT3L during cell division. We propose a model in which specification to the DC lineage is driven by parallel and inheritable transcriptional programs in HSCs and is reinforced over cell division by recursive interactions between transcriptional programs and extrinsic signals.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Lee J,Zhou YJ,Ma W,Zhang W,Aljoufi A,Luh T,Lucero K,Liang D,Thomsen M,Bhagat G,Shen Y,Liu Kdoi
10.1038/ni.3789subject
Has Abstractpub_date
2017-08-01 00:00:00pages
877-888issue
8eissn
1529-2908issn
1529-2916pii
ni.3789journal_volume
18pub_type
杂志文章abstract::Autophagosomes delivers cytoplasmic constituents to lysosomes for degradation, whereas inflammasomes are molecular platforms activated by infection or stress that regulate the activity of caspase-1 and the maturation of interleukin 1β (IL-1β) and IL-18. Here we show that the induction of AIM2 or NLRP3 inflammasomes in...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2215
更新日期:2012-01-29 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::The lung is inhabited by resident alveolar and interstitial macrophages as well as monocytic cells that survey lung tissues. Each cell type plays distinct functional roles under homeostatic and inflammatory conditions, but mechanisms establishing their molecular identities and functional potential remain poorly unders...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0582-z
更新日期:2020-02-01 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
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3053
更新日期:2015-02-01 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::The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), tha...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0698-1
更新日期:2020-07-01 00:00:00
abstract::Cytosolic detection of pathogen-derived nucleic acids is critical for the initiation of innate immune defense against diverse bacterial, viral and eukaryotic pathogens. Conversely, inappropriate responses to cytosolic nucleic acids can produce severe autoimmune pathology. The host protein STING has been identified as ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni.2491
更新日期:2013-01-01 00:00:00
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1271
更新日期:2005-12-01 00:00:00
abstract::Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR)...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/86302
更新日期:2001-04-01 00:00:00
abstract:: ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-018-0247-3
更新日期:2018-11-01 00:00:00
abstract::The active ubiquitin E3 ligase GRAIL is crucial in the induction of CD4 T cell anergy. Here we show that GRAIL is associated with and regulated by two isoforms of the ubiquitin-specific protease otubain 1. In lethally irradiated mice reconstituted with bone marrow cells from T cell receptor-transgenic mice retrovirall...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1017
更新日期:2004-01-01 00:00:00
abstract::The mouse protein Qa-1 (HLA-E in humans) is essential for immunological protection and immune regulation. Although Qa-1 has been linked to CD8 T cell-dependent suppression, the physiological relevance of this observation is unclear. We generated mice deficient in Qa-1 to develop an understanding of this process. Qa-1-...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1063
更新日期:2004-05-01 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::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/s41590-020-0739-9
更新日期:2020-08-01 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: 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::CD4+ T cell priming under T helper type I (T(H)1) or T(H)2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation p...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni872
更新日期:2003-01-01 00:00:00
abstract::Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone marrow stromal cell types. Here we identified rare activated bone marrow monocytes and macrophages with high expression of α-smooth muscle actin (α-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs. These myeloid cells ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2408
更新日期:2012-11-01 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
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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
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0347-8
更新日期:2019-05-01 00:00:00
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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
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journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1438
更新日期:2007-03-01 00:00:00
abstract::Microbial infections often precede the onset of autoimmunity. How infections trigger autoimmunity remains poorly understood. We investigated the possibility that infection might create conditions that allow the stimulatory presentation of self peptides themselves and that this might suffice to elicit autoreactive T ce...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3512
更新日期:2016-09-01 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::Indoleamine 2,3 dioxygenase (IDO) activity during pregnancy protects developing fetuses from maternal immune responses in CBA mice. We show here that fetal allografts were rejected only in mating combinations where paternally inherited tissue antigens elicited potent maternal T cell responses after exposure to IDO inh...
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::Regulatory T (Treg) cells respond to immune and inflammatory signals to mediate immunosuppression, but how the functional integrity of Treg cells is maintained under activating environments is unclear. Here we show that autophagy is active in Treg cells and supports their lineage stability and survival fitness. Treg c...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3365
更新日期:2016-03-01 00:00:00
abstract::Dynamic changes in the expression of transcription factors (TFs) can influence the specification of distinct CD8+ T cell fates, but the observation of equivalent expression of TFs among differentially fated precursor cells suggests additional underlying mechanisms. Here we profiled the genome-wide histone modification...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.3706
更新日期:2017-05-01 00:00:00
abstract::Mast cell activation induced by aggregation of Fc epsilon RI receptors with immunoglobulin E and antigen is mediated through the activation of multiple protein kinase cascades. Here we report that the regulatory protein RabGEF1 bound to Ras and negatively regulated Ras activation and its 'downstream' effector pathways...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1093
更新日期:2004-08-01 00:00:00