Abstract:
:High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that confer antigen specificity. Here, we present a strategy that enables simultaneous analysis of TCR sequences and corresponding full transcriptomes from 3'-barcoded scRNA-seq samples. This approach is compatible with common 3' scRNA-seq methods, and adaptable to processed samples post hoc. We applied the technique to identify transcriptional signatures associated with T cells sharing common TCRs from immunized mice and from patients with food allergy. We observed preferential phenotypes among subsets of expanded clonotypes, including type 2 helper CD4+ T cell (TH2) states associated with food allergy. These results demonstrate the utility of our method when studying diseases in which clonotype-driven responses are critical to understanding the underlying biology.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Tu AA,Gierahn TM,Monian B,Morgan DM,Mehta NK,Ruiter B,Shreffler WG,Shalek AK,Love JCdoi
10.1038/s41590-019-0544-5subject
Has Abstractpub_date
2019-12-01 00:00:00pages
1692-1699issue
12eissn
1529-2908issn
1529-2916pii
10.1038/s41590-019-0544-5journal_volume
20pub_type
杂志文章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::Phagocytosis has essential functions in immunity. Here we highlight the presence of a subcellular level of self-non-self discrimination in dendritic cells that operates at the level of individual phagosomes. We discuss how engagement of Toll-like receptor signaling controls distinct programs of phagosome maturation. A...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1006-1029
更新日期:2006-10-01 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::CD8+ T cells play an important role in immunity to viruses. Just how important these cells are is demonstrated by the evolution of viral strategies for blocking the generation or display of peptide-major histocompatibility complex class I complexes on the surfaces of virus-infected cells. Here, we focus on viral inter...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1102-1019
更新日期:2002-11-01 00:00:00
abstract::Progenitor-like CD8+ T cells mediate long-term immunity to chronic infection and cancer and respond potently to immune checkpoint blockade. These cells share transcriptional regulators with memory precursor cells, including T cell-specific transcription factor 1 (TCF1), but it is unclear whether they adopt distinct pr...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0403-4
更新日期:2019-07-01 00:00:00
abstract::DAP12-coupled receptors influence signals emanating from Toll-like receptors, integrins and receptors for cytokines and growth factors. New findings indicate that DAP12 also facilitates the ability of CSF-1R, the receptor for M-CSF, to induce the stabilization and nuclear translocation of beta-catenin. ...
journal_title:Nature immunology
pub_type: 新闻
doi:10.1038/ni0709-681
更新日期:2009-07-01 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::Xenogeneic tissues induce vigorous T cell immunity, reflecting the ability of costimulatory molecules to function across species barriers. We describe a strategy to inhibit costimulation that exploits species differences using the model of porcine pancreatic islet transplantation into mice. Mice were immunized with ch...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/77853
更新日期:2000-08-01 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 a result of decades of research-driven breakthroughs in basic and clinical science and recent advances in the broad-scale implementation of interventions for the prevention and treatment of infection with HIV, a turning point has been reached in the global HIV-AIDS pandemic. To end the pandemic and achieve the goal...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2735
更新日期:2013-11-01 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
pub_type: 杂志文章,评审
doi:10.1038/ni.3273
更新日期:2015-10-01 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::Plant proteins belonging to the nucleotide-binding site-leucine-rich repeat (NBS-LRR) family are used for pathogen detection. Like the mammalian Nod-LRR protein 'sensors' that detect intracellular conserved pathogen-associated molecular patterns, plant NBS-LRR proteins detect pathogen-associated proteins, most often t...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1410
更新日期:2006-12-01 00:00:00
abstract::Tumor necrosis factor receptor 1 (TNFR1)-associated death domain protein (TRADD) is essential in recruiting signaling molecules to the TNFR1 receptor complex. Interferon-gamma (IFN-gamma) is a potent activator of macrophages and uses signal transducer and activator of transcription 1-alpha (STAT1-alpha) for signal tra...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni1025
更新日期:2004-02-01 00:00:00
abstract::CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gen...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni759
更新日期:2002-02-01 00:00:00
abstract::CD8+ T cells responding to chronic infections or tumors acquire an 'exhausted' state associated with elevated expression of inhibitory receptors, including PD-1, and impaired cytokine production. Exhausted T cells are continuously replenished by T cells with precursor characteristics that self-renew and depend on the ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0760-z
更新日期:2020-10-01 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::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::Type I natural killer T cells (NKT cells) are characterized by an invariant variable region 14-joining region 18 (V(α)14-J(α)18) T cell antigen receptor (TCR) α-chain and recognition of the glycolipid α-galactosylceramide (α-GalCer) restricted to the antigen-presenting molecule CD1d. Here we describe a population of α...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni.2051
更新日期:2011-06-12 00:00:00
abstract::Naturally arising CD25(+)CD4(+) regulatory T cells actively maintain immunological self-tolerance. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. A reduction in their number or function can also elicit tumor immunity, whereas their antigen-specific population expansion can establish ...
journal_title:Nature immunology
pub_type: 杂志文章,评审
doi:10.1038/ni1178
更新日期:2005-04-01 00:00:00
abstract::The transcription factor BATF directly regulates key components of the formation and function of follicular helper T cells and antibody class switching in B cells. ...
journal_title:Nature immunology
pub_type: 评论,新闻
doi:10.1038/ni.2042
更新日期:2011-06-01 00:00:00
abstract::αβ T cell antigen receptors (TCRs) bind complexes of peptide and major histocompatibility complex (pMHC) with low affinity, which poses a considerable challenge for the direct identification of αβ T cell cognate peptides. Here we describe a platform for the discovery of MHC class II epitopes based on the screening of ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-019-0335-z
更新日期:2019-05-01 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::Bacterial lipopolysaccharide triggers human caspase-4 (murine caspase-11) to cleave gasdermin-D and induce pyroptotic cell death. How lipopolysaccharide sequestered in the membranes of cytosol-invading bacteria activates caspases remains unknown. Here we show that in interferon-γ-stimulated cells guanylate-binding pro...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/s41590-020-0697-2
更新日期:2020-08-01 00:00:00
abstract::Mice deficient for paired immunoglobulin (Ig)-like receptor B (PIR-B) show defective regulation of receptor-mediated activation in antigen-presenting cells. Older PIR-B(-/-) mice had an increased number of peritoneal B1 cells. Splenic PIR-B(-/-) B2 cells were constitutively activated and proliferated much more than th...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni801
更新日期:2002-06-01 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::CD46 is a widely expressed transmembrane protein that was initially identified as binding and inactivating C3b and C4b complement products. We used mice that were transgenic for one of two human CD46 isoforms that differ in their cytoplasmic domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation ...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni810
更新日期:2002-07-01 00:00:00
abstract::Chemoattractant-stimulated granule release from neutrophils, basophils and eosinophils is critical for the innate immune response against infectious bacteria. Interleukin 8 (IL-8) activation of the chemokine receptor CXCRI was found to stimulate rapid formation of beta-arrestin complexes with Hck or c-Fgr. Formation o...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/79767
更新日期:2000-09-01 00:00:00
abstract::Phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN) phosphatase serve essential functions in the regulation of cell growth, differentiation and survival by modulating intracellular phosphatidylinositol-3,4,5-trisphosphate (PI-3,4,5-P3) concentrations. Here we show that the conditional deletion o...
journal_title:Nature immunology
pub_type: 杂志文章
doi:10.1038/ni892
更新日期:2003-03-01 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