Abstract:
:Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions, are not merely extruded to maintain homeostatic cell numbers, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4+ T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4+ T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.
journal_name
Naturejournal_title
Natureauthors
Cummings RJ,Barbet G,Bongers G,Hartmann BM,Gettler K,Muniz L,Furtado GC,Cho J,Lira SA,Blander JMdoi
10.1038/nature20138subject
Has Abstractpub_date
2016-11-24 00:00:00pages
565-569issue
7630eissn
0028-0836issn
1476-4687pii
nature20138journal_volume
539pub_type
杂志文章相关文献
NATURE文献大全abstract::Interest in mapping the global distribution of malaria is motivated by a need to define populations at risk for appropriate resource allocation and to provide a robust framework for evaluating its global economic impact. Comparison of older and more recent malaria maps shows how the disease has been geographically res...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03342
更新日期:2005-03-10 00:00:00
abstract::Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore 'biological-activity space'. ...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature03196
更新日期:2004-12-16 00:00:00
abstract::Monoclonal antibodies were raised against antibodies to distinct carboxy-terminal KDEL sequences of two soluble, resident endoplasmic reticulum proteins. These anti-idiotype reagents recognize an intrinsic membrane protein with characteristics expected of a receptor responsible for the recognition and return of reside...
journal_title:Nature
pub_type: 杂志文章,收录出版
doi:10.1038/345495a0
更新日期:1990-06-07 00:00:00
abstract::The age of dense interstellar cloud cores, where stars and planets form, is a crucial parameter in star formation and difficult to measure. Some models predict rapid collapse, whereas others predict timescales of more than one million years (ref. 3). One possible approach to determining the age is through chemical cha...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13924
更新日期:2014-12-11 00:00:00
abstract::The response of the terrestrial carbon cycle to climate change is among the largest uncertainties affecting future climate change projections. The feedback between the terrestrial carbon cycle and climate is partly determined by changes in the turnover time of carbon in land ecosystems, which in turn is an ecosystem p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13731
更新日期:2014-10-09 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07480-0
更新日期:2018-11-01 00:00:00
abstract::It has been suggested that the initiation step in mouse skin carcinogenesis involves an alteration in epidermal-differentiation, as mouse basal keratinocytes exposed to initiators resist the arrest of cell growth that is normally associated with the induction of terminal differentiation by calcium ions. The growth of ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/314459a0
更新日期:1985-04-04 00:00:00
abstract::Io leaves a magnetic footprint on Jupiter's upper atmosphere that appears as a spot of ultraviolet emission that remains fixed underneath Io as Jupiter rotates. The specific physical mechanisms responsible for generating those emissions are not well understood, but in general the spot seems to arise because of an elec...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/415997a
更新日期:2002-02-28 00:00:00
abstract::Helminth parasitic infections are a major global health and social burden. The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus produ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16527
更新日期:2016-01-14 00:00:00
abstract::Among the ten subtypes of mammalian voltage-gated calcium (Cav) channels, Cav3.1-Cav3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain1-5. Here we report the cryo-electron microscopy structures of human Cav3....
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1801-3
更新日期:2019-12-01 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07324-x
更新日期:2018-11-01 00:00:00
abstract::Distrust in scientific expertise1-14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2-4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2281-1
更新日期:2020-06-01 00:00:00
abstract::Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16067
更新日期:2015-12-03 00:00:00
abstract::Protecting the world's freshwater resources requires diagnosing threats over a broad range of scales, from global to local. Here we present the first worldwide synthesis to jointly consider human and biodiversity perspectives on water security using a spatial framework that quantifies multiple stressors and accounts f...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09440
更新日期:2010-09-30 00:00:00
abstract::Cells sense the context in which they grow to adapt their phenotype and allow multicellular patterning by mechanisms of autocrine and paracrine signalling. However, patterns also form in cell populations exposed to the same signalling molecules and substratum, which often correlate with specific features of the popula...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14429
更新日期:2015-07-02 00:00:00
abstract::Interferon-induced proteins with tetratricopeptide repeats (IFITs) are innate immune effector molecules that are thought to confer antiviral defence through disruption of protein-protein interactions in the host translation-initiation machinery. However, it was recently discovered that IFITs can directly recognize vir...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11783
更新日期:2013-02-07 00:00:00
abstract::The ability to process microbial antigens and present them at the surface of cells is an important aspect of our innate ability to clear infections. It is generally accepted that antigens in the cytoplasm are loaded in the endoplasmic reticulum and presented at the cell surface on major histocompatibility complex (MHC...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01912
更新日期:2003-09-25 00:00:00
abstract::DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13899
更新日期:2015-01-29 00:00:00
abstract::The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is a gamma-2 herpesvirus that is implicated in the pathogenesis of Kaposi's sarcoma and of primary effusion B-cell lymphomas (PELs). KSHV infects malignant and progenitor cells of Kaposi's sarcoma and PEL, it encodes putative oncogenes and genes that may cause Ka...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/34193
更新日期:1998-01-01 00:00:00
abstract::7SL RNA is an abundant cytoplasmic RNA which functions in protein secretion as a component of the signal recognition particle. Alu sequences are the most abundant family of human and rodent middle repetitive DNA sequences (reviewed in ref. 2). The primary structure of human 7SL RNA consists of an Alu sequence interrup...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/312171a0
更新日期:1984-11-08 00:00:00
abstract::Molecular self-assembly offers a 'bottom-up' route to fabrication with subnanometre precision of complex structures from simple components. DNA has proved to be a versatile building block for programmable construction of such objects, including two-dimensional crystals, nanotubes, and three-dimensional wireframe nanop...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08016
更新日期:2009-05-21 00:00:00
abstract::The interaction of lectins with carbohydrate receptors on the plasma membrane of eukaryotic cells results in a wide variety of biological effects. One effect which has been extensively studied is the stimulation of lymphocytes to blastogenesis and proliferation. High doses of concanavalin A (Con A) and phytohaemagglut...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/284273a0
更新日期:1980-03-20 00:00:00
abstract::Topoisomerases relieve the torsional strain in DNA that is built up during replication and transcription. They are vital for cell proliferation and are a target for poisoning by anti-cancer drugs. Type IB topoisomerase (TopIB) forms a protein clamp around the DNA duplex and creates a transient nick that permits remova...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03395
更新日期:2005-03-31 00:00:00
abstract::During puberty, the mouse mammary gland develops into a highly branched epithelial network. Owing to the absence of exclusive stem cell markers, the location, multiplicity, dynamics and fate of mammary stem cells (MaSCs), which drive branching morphogenesis, are unknown. Here we show that morphogenesis is driven by pr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature21046
更新日期:2017-02-16 00:00:00
abstract::It is generally accepted that the specific function of a gene depends on its coding sequence. The three paired-box and homeobox genes paired (prd), gooseberry (gsb) and gooseberry neuro (gsbn) have distinct developmental functions in Drosophila embryogenesis. During the syncytial blastoderm stage, the pair-rule gene p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/367083a0
更新日期:1994-01-06 00:00:00
abstract::The origin of eukaryotes stands as a major conundrum in biology. Current evidence indicates that the last eukaryotic common ancestor already possessed many eukaryotic hallmarks, including a complex subcellular organization. In addition, the lack of evolutionary intermediates challenges the elucidation of the relative ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16941
更新日期:2016-03-03 00:00:00
abstract::The neuronal structure and connectivity underlying receptive field organisation of cells in the cat visual cortex have been investigated. Intracellular recordings were made using a micropipette filled with a histochemical marker, which was injected into the cells after their receptive fields had been characterised. Th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/280120a0
更新日期:1979-07-12 00:00:00
abstract::Ecological theory suggests that large-scale patterns such as community stability can be influenced by changes in interspecific interactions that arise from the behavioural and/or physiological responses of individual species varying over time. Although this theory has experimental support, evidence from natural ecosys...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25504
更新日期:2018-02-15 00:00:00
abstract::Integrins are a superfamily of related molecules whose function, where known, is to mediate adhesion. The so-called very-late-activation antigen (VLA) family includes at least five distinct heterodimers, each composed of a unique alpha-subunit non-covalently associated with a common beta-subunit. Several members of th...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/339152a0
更新日期:1989-05-11 00:00:00
abstract::Most normal mammalian cells have a finite lifespan, thought to constitute a protective mechanism against unlimited proliferation. This phenomenon, called senescence, is driven by telomere attrition, which triggers the induction of tumour suppressors including p16(INK4a) (ref. 5). In cultured cells, senescence can be e...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03890
更新日期:2005-08-04 00:00:00