Abstract:
:Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the survival of NK-22 cells and IL-22 production in response to IL-23 but was insufficient to induce robust expansion. Proliferation of NK-22 cells was increased markedly by adding either IL-1beta or IL-2 to IL-7 and was even stronger in the presence of IL-1beta plus IL-2. In contrast to IL-7, continuous culture in IL-1beta and IL-2 modified NK-22 cytokine profiles. IL-1beta promoted constitutive IL-22 secretion rather than acute IL-22 production in response to IL-23 and induced IL-17 in some cells. IL-2 reduced secretion of IL-22 and IL-17, increasing production of IFN-gamma and leukemia inhibitory factor. Functional deviation toward IFN-gamma production also was induced by continuous culture in IL-23. These results demonstrate the functional plasticity of NK-22 cells, which may allow flexible responses to different pathogens. Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell-mediated mucosal immunity.
journal_name
Proc Natl Acad Sci U S Aauthors
Cella M,Otero K,Colonna Mdoi
10.1073/pnas.1005641107subject
Has Abstractpub_date
2010-06-15 00:00:00pages
10961-6issue
24eissn
0027-8424issn
1091-6490pii
1005641107journal_volume
107pub_type
杂志文章abstract::Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*i(1/4)...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0913439107
更新日期:2010-03-16 00:00:00
abstract::The F-box represents a protein motif originally identified as a conserved amino-terminal domain within the Neurospora crassa negative regulator sulfur controller-2. Recently, F-boxes have been found within a number of cell cycle regulatory proteins, where they mediate ubiquitin-driven proteolytic events required for m...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.5.2417
更新日期:1998-03-03 00:00:00
abstract::Plasma of normal human individuals was shown to contain an inhibitor of Trypanosoma cruzi neuraminidase (NAase; acylneuraminyl hydrolase, sialidase, EC 3.2.1.18). The inhibitor has been purified to homogeneity by PEG precipitation, CM Affi-Gel Blue Sepharose chromatography, and gel filtration. The purified preparation...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.10.3097
更新日期:1987-05-01 00:00:00
abstract::Accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR), an intracellular signaling pathway that adjusts the protein folding capacity of the ER according to need. If homeostasis in the ER protein folding environment cannot be reestablished, cells commit to apop...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1010580107
更新日期:2010-09-14 00:00:00
abstract::Ionizing radiation has been used to selectively separate the circadian oscillator function of the eye of Aplysia from some of its other functions--synchronous compound action potential (CAP) generation, the light response, synaptic transmission between photoreceptors and output neurons, and the bursting pacemaker mech...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.9.5542
更新日期:1980-09-01 00:00:00
abstract::Antibody modulation of T-cell coinhibitory (e.g., CTLA-4) or costimulatory (e.g., 4-1BB) receptors promotes clinical responses to a variety of cancers. Therapeutic cancer vaccination, in contrast, has produced limited clinical benefit and no curative therapies. The E6 and E7 oncoproteins of human papilloma virus (HPV)...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1514418112
更新日期:2015-09-22 00:00:00
abstract::Chemical cross-linking mass spectrometry (CXMS) is being increasingly used to study protein assemblies and complex protein interaction networks. Existing CXMS chemical cross-linkers target only Lys, Cys, Glu, and Asp residues, limiting the information measurable. Here we report a "plant-and-cast" cross-linking strateg...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1813574115
更新日期:2018-10-30 00:00:00
abstract::Human cancer cells with a mutated p53 tumor-suppressor gene have a selective growth advantage and may exhibit resistance to ionizing radiation and certain chemotherapeutic agents. To examine the prognostic value of mutations in the p53 gene, a cohort of 90 Midwestern Caucasian breast cancer patients were analyzed with...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.3.1093
更新日期:1996-02-06 00:00:00
abstract::Fetal exposure to environmental insults increases the susceptibility to late-onset neuropsychiatric disorders. Alcohol is listed as one of such prenatal environmental risk factors and known to exert devastating teratogenetic effects on the developing brain, leading to complex neurological and psychiatric symptoms obse...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1100903108
更新日期:2011-03-08 00:00:00
abstract::HU, the major DNA binding protein of Escherichia coli, exists in solution as a heterodimer composed of two highly homologous subunits: HU1, encoded by hupB; HU2, encoded by hupA. The purification of the HU protein from hupA- or hupB- bacteria showed that the hupB mutant strains synthesize normal amounts of the HU2 sub...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.20.7691
更新日期:1989-10-01 00:00:00
abstract::Inbred 129 strain mice are predisposed to developing male germ cell tumors (GCTs) of the testes. The inherent genetic defects that underlie male GCT susceptibility in the 129 mouse strain are unknown. GCT incidence is increased in 129 strain males that lack functional p53 protein, and we have used this finding to faci...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.140208197
更新日期:2000-07-18 00:00:00
abstract::Major changes in global rainfall patterns accompanied a northward shift of Earth's thermal equator at the onset of an abrupt climate change 14.6 kya. This northward pull of Earth's wind and rain belts stemmed from disintegration of North Atlantic winter sea ice cover, which steepened the interhemispheric meridional te...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1301855110
更新日期:2013-10-15 00:00:00
abstract::Sirtuin 2 (SIRT2) is a sirtuin family deacetylase that directs acetylome signaling, protects genome integrity, and is a murine tumor suppressor. We show that SIRT2 directs replication stress responses by regulating the activity of cyclin-dependent kinase 9 (CDK9), a protein required for recovery from replication arres...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1301463110
更新日期:2013-08-13 00:00:00
abstract::Wnts regulate important intracellular signaling events, and dysregulation of the Wnt pathway has been linked to human disease. Here, we uncover numerous Wnt canonical effectors in human platelets where Wnts, their receptors, and downstream signaling components have not been previously described. We demonstrate that th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0906268106
更新日期:2009-11-24 00:00:00
abstract::A monoclonal antibody has been developed that recognizes a mouse lymphocyte antigen, Ly-23, that is controlled by an H-3 histocompatibility complex-linked gene on the second chromosome. Competitive binding experiments demonstrate that this antigen is distinct from the polymorphic beta 2-microglobulin antigen, which al...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.21.6620
更新日期:1983-11-01 00:00:00
abstract::Global warming is expected to lead to a large increase in atmospheric water vapor content and to changes in the hydrological cycle, which include an intensification of precipitation extremes. The intensity of precipitation extremes is widely held to increase proportionately to the increase in atmospheric water vapor c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0907610106
更新日期:2009-09-01 00:00:00
abstract::The antigenic mosaic of the Archaebacterium Methanobacterium thermoautotrophicum, strain delta H, was analyzed with a panel of six monoclonal antibodies. Five antigenic determinants were identified. One contains N-acetyl-D-glucosamine, another contains N-acetyl-D-galactosamine, and a third contains gamma-glutamylalani...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.20.6346
更新日期:1983-10-01 00:00:00
abstract::Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked mu, delta, and kappa opioid receptors. One major effector for these receptors is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the te...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0508812103
更新日期:2006-03-07 00:00:00
abstract::A number of distressing trends, including a decline in the share of key research grants going to younger scientists, as well as a steady rise in the age at which investigators receive their first funding, are now a decades-long feature of the US biomedical research workforce. Working committees have proposed recommend...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1418761112
更新日期:2015-01-13 00:00:00
abstract::The fluorescence properties of GFP are strongly influenced by the protonation states of its chromophore and nearby amino acid side chains. In the ground state, the GFP chromophore is neutral and absorbs in the near UV. Upon excitation, the chromophore is deprotonated, and the resulting anionic chromophore emits its gr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0404262102
更新日期:2004-12-28 00:00:00
abstract::Translocation of proteins across the mitochondrial inner membrane is an essential process requiring an import motor having mitochondrial Hsp70 (mtHsp70) at its core. The J protein partner of mtHsp70, Pam18, is an integral part of this motor, serving to stimulate the ATPase activity of mtHsp70. Pam16, an essential prot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0505969102
更新日期:2005-08-30 00:00:00
abstract::Resting-state functional connectivity is used throughout neuroscience to study brain organization and to generate biomarkers of development, disease, and cognition. The processes that give rise to correlated activity are, however, poorly understood. Here we decompose resting-state functional connectivity using a tempo...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2005531117
更新日期:2020-11-10 00:00:00
abstract::Vertebrates, from zebra fish to humans, have an innate immune recognition of many bacterial flagellins. This involves a conserved eight-amino acid epitope in flagellin recognized by the Toll-like receptor 5 (TLR5). Several important human pathogens, such as Helicobacter pylori and Campylobacter jejuni, have escaped TL...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2010996117
更新日期:2020-07-21 00:00:00
abstract::Recent data indicate that sustained elevations in plasma insulin suppress the mRNA for IRS-2, a component of the insulin signaling pathway in liver, and that this deficiency contributes to hepatic insulin resistance and inappropriate gluconeogenesis. Here, we use nuclear run-on assays to show that insulin inhibits tra...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.071054598
更新日期:2001-03-27 00:00:00
abstract::Uncoupling protein 1 (UCP1) catalyzes fatty acid-activated, purine nucleotide-sensitive proton leak across the mitochondrial inner membrane of brown adipose tissue to produce heat, and could help combat obesity and metabolic disease in humans. Studies over the last 30 years conclude that the protein is a dimer, bindin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1503833112
更新日期:2015-06-02 00:00:00
abstract::A microfluidic mixer is applied to study the kinetics of calmodulin conformational changes upon Ca2+ binding. The device facilitates rapid, uniform mixing by decoupling hydrodynamic focusing from diffusive mixing and accesses time scales of tens of microseconds. The mixer is used in conjunction with multiphoton micros...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0710810105
更新日期:2008-01-15 00:00:00
abstract::Staphylococcus aureus is a major cause of community-acquired and nosocomial infections including the life-threatening conditions endocarditis, necrotizing pneumonia, necrotizing fasciitis, and septicemia. Toll-like receptor (TLR)-2, a membrane-bound microbial sensor, detects staphylococcal components, but macrophages ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904958106
更新日期:2009-08-04 00:00:00
abstract::Schizosaccharomyces pombe cells were transformed with an S. pombe expression vector containing a full-length cDNA of the Chlorella hexose transporter. The transformed cells accumulated 3-O-methylglucose up to 10-fold, whereas wild-type S. pombe and control transformants could only equilibrate this sugar analogue. In a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.20.7949
更新日期:1990-10-01 00:00:00
abstract::Class I phosphoinositide 3-kinase contains four isoforms of the catalytic subunit, p110alpha, -beta, -gamma, and -delta. At physiological levels of expression, the wild-type p110alpha isoform lacks oncogenic potential, but gain-of-function mutations and overexpression of p110alpha are correlated with oncogenicity. The...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0510772103
更新日期:2006-01-31 00:00:00
abstract::The rise of inorganic-biological hybrid organisms for solar-to-chemical production has spurred mechanistic investigations into the dynamics of the biotic-abiotic interface to drive the development of next-generation systems. The model system, Moorella thermoacetica-cadmium sulfide (CdS), combines an inorganic semicond...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1610554113
更新日期:2016-10-18 00:00:00