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Nature Immunology

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https://www.readbyqxmd.com/read/28319098/irap-endosomes-restrict-tlr9-activation-and-signaling
#1
Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury, Loredana Saveanu
The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP(+) endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP(+) endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection...
March 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28319097/long-noncoding-rna-lnckdm2b-is-required-for-ilc3-maintenance-by-initiation-of-zfp292-expression
#2
Benyu Liu, Buqing Ye, Liuliu Yang, Xiaoxiao Zhu, Guanling Huang, Pingping Zhu, Ying Du, Jiayi Wu, Xiwen Qin, Runsheng Chen, Yong Tian, Zusen Fan
Innate lymphoid cells (ILCs) communicate with other hematopoietic and nonhematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How ILC lineages develop and are maintained remains largely unknown. In this study we observed that a divergent long noncoding RNA (lncRNA), lncKdm2b, was expressed at high levels in intestinal group 3 ILCs (ILC3s). LncKdm2b deficiency in the hematopoietic system led to reductions in the number and effector functions of ILC3s. LncKdm2b expression sustained the maintenance of ILC3s by promoting their proliferation through activation of the transcription factor Zfp292...
March 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28288101/opposing-macrophage-polarization-programs-show-extensive-epigenomic-and-transcriptional-cross-talk
#3
Viviana Piccolo, Alessia Curina, Marco Genua, Serena Ghisletti, Marta Simonatto, Arianna Sabò, Bruno Amati, Renato Ostuni, Gioacchino Natoli
Stimulation of macrophages with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer, macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited the epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while binding motifs for the transcription factors STAT1 and IRF1 were associated with robust and IL-4-resistant responses to IFN-γ, their coexistence with binding sites for auxiliary transcription factors such as AP-1 generated vulnerability to IL-4-mediated inhibition...
March 13, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28288100/epigenetic-landscapes-reveal-transcription-factors-that-regulate-cd8-t-cell-differentiation
#4
Bingfei Yu, Kai Zhang, J Justin Milner, Clara Toma, Runqiang Chen, James P Scott-Browne, Renata M Pereira, Shane Crotty, John T Chang, Matthew E Pipkin, Wei Wang, Ananda W Goldrath
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 modifications, open chromatin and gene expression of naive, terminal-effector, memory-precursor and memory CD8(+) T cell populations induced during the in vivo response to bacterial infection. Integration of these data suggested that the expression and binding of TFs contributed to the establishment of subset-specific enhancers during differentiation...
March 13, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28288099/nlrp12-attenuates-colon-inflammation-by-maintaining-colonic-microbial-diversity-and-promoting-protective-commensal-bacterial-growth
#5
Liang Chen, Justin E Wilson, Mark J Koenigsknecht, Wei-Chun Chou, Stephanie A Montgomery, Agnieszka D Truax, W June Brickey, Christopher D Packey, Nitsan Maharshak, Glenn K Matsushima, Scott E Plevy, Vincent B Young, R Balfour Sartor, Jenny P-Y Ting
Inflammatory bowel diseases involve the dynamic interaction of host genetics, the microbiome and inflammatory responses. Here we found lower expression of NLRP12 (which encodes a negative regulator of innate immunity) in human ulcerative colitis, by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12 deficiency in mice caused increased basal colonic inflammation, which led to a less-diverse microbiome and loss of protective gut commensal strains (of the family Lachnospiraceae) and a greater abundance of colitogenic strains (of the family Erysipelotrichaceae)...
March 13, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28263321/social-network-architecture-of-human-immune-cells-unveiled-by-quantitative-proteomics
#6
Jan C Rieckmann, Roger Geiger, Daniel Hornburg, Tobias Wolf, Ksenya Kveler, David Jarrossay, Federica Sallusto, Shai S Shen-Orr, Antonio Lanzavecchia, Matthias Mann, Felix Meissner
The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of >10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, thereby connecting distinct immune functions...
March 6, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28218745/human-%C3%AE-%C3%AE-t-cells-are-quickly-reconstituted-after-stem-cell-transplantation-and-show-adaptive-clonal-expansion-in-response-to-viral-infection
#7
Sarina Ravens, Christian Schultze-Florey, Solaiman Raha, Inga Sandrock, Melanie Drenker, Linda Oberdörfer, Annika Reinhardt, Inga Ravens, Maleen Beck, Robert Geffers, Constantin von Kaisenberg, Michael Heuser, Felicitas Thol, Arnold Ganser, Reinhold Förster, Christian Koenecke, Immo Prinz
To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires were private...
February 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28250425/essential-role-for-the-transcription-factor-bhlhe41-in-regulating-the-development-self-renewal-and-bcr-repertoire-of-b-1a-cells
#8
Taras Kreslavsky, Bojan Vilagos, Hiromi Tagoh, Daniela Kostanova Poliakova, Tanja A Schwickert, Miriam Wöhner, Markus Jaritz, Siegfried Weiss, Reshma Taneja, Moritz J Rossner, Meinrad Busslinger
Innate-like B-1a cells provide a first line of defense against pathogens, yet little is known about their transcriptional control. Here we identified an essential role for the transcription factor Bhlhe41, with a lesser contribution by Bhlhe40, in controlling B-1a cell differentiation. Bhlhe41(-/-)Bhlhe40(-/-) B-1a cells were present at much lower abundance than were their wild-type counterparts. Mutant B-1a cells exhibited an abnormal cell-surface phenotype and altered B cell receptor (BCR) repertoire exemplified by loss of the phosphatidylcholine-specific VH12Vκ4 BCR...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28250424/themis-enhances-tcr-signaling-and-enables-positive-selection-by-selective-inhibition-of-the-phosphatase-shp-1
#9
Seeyoung Choi, Claude Warzecha, Ekaterina Zvezdova, Jan Lee, Jérémy Argenty, Renaud Lesourne, L Aravind, Paul E Love
THEMIS, a T cell-specific protein with high expression in CD4(+)CD8(+) thymocytes, has a crucial role in positive selection and T cell development. THEMIS lacks defined catalytic domains but contains two tandem repeats of a distinctive module of unknown function (CABIT). Here we found that THEMIS directly regulated the catalytic activity of the tyrosine phosphatase SHP-1. This action was mediated by the CABIT modules, which bound to the phosphatase domain of SHP-1 and promoted or stabilized oxidation of SHP-1's catalytic cysteine residue, which inhibited the tyrosine-phosphatase activity of SHP-1...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28218746/early-transcriptional-and-epigenetic-regulation-of-cd8-t-cell-differentiation-revealed-by-single-cell-rna-sequencing
#10
Boyko Kakaradov, Janilyn Arsenio, Christella E Widjaja, Zhaoren He, Stefan Aigner, Patrick J Metz, Bingfei Yu, Ellen J Wehrens, Justine Lopez, Stephanie H Kim, Elina I Zuniga, Ananda W Goldrath, John T Chang, Gene W Yeo
During microbial infection, responding CD8(+) T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA-sequencing approach and analyzed individual CD8(+) T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants that controlled the fate specification of CD8(+) T lymphocytes...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28192418/defining-the-antibody-cross-reactome-directed-against-the-influenza-virus-surface-glycoproteins
#11
Raffael Nachbagauer, Angela Choi, Ariana Hirsh, Irina Margine, Sayaka Iida, Aldo Barrera, Marcela Ferres, Randy A Albrecht, Adolfo García-Sastre, Nicole M Bouvier, Kimihito Ito, Rafael A Medina, Peter Palese, Florian Krammer
Infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. To assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent H1N1 or H3N2 subtypes of influenza virus. We measured antibody responses by ELISA of an extensive panel of recombinant glycoproteins representing the viral diversity in nature. Guinea pigs developed high titers of broadly cross-reactive antibodies; mice and ferrets exhibited narrower humoral responses...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28192417/defining-b-cell-immunodominance-to-viruses
#12
Davide Angeletti, James S Gibbs, Matthew Angel, Ivan Kosik, Heather D Hickman, Gregory M Frank, Suman R Das, Adam K Wheatley, Madhu Prabhakaran, David J Leggat, Adrian B McDermott, Jonathan W Yewdell
Immunodominance (ID) defines the hierarchical immune response to competing antigens in complex immunogens. Little is known regarding B cell and antibody ID despite its importance in immunity to viruses and other pathogens. We show that B cells and serum antibodies from inbred mice demonstrate a reproducible ID hierarchy to the five major antigenic sites in the influenza A virus hemagglutinin globular domain. The hierarchy changed as the immune response progressed, and it was dependent on antigen formulation and delivery...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28166218/critical-role-of-irf1-and-batf-in-forming-chromatin-landscape-during-type-1-regulatory-cell-differentiation
#13
Katarzyna Karwacz, Emily R Miraldi, Maria Pokrovskii, Asaf Madi, Nir Yosef, Ivo Wortman, Xi Chen, Aaron Watters, Nicholas Carriero, Amit Awasthi, Aviv Regev, Richard Bonneau, Dan Littman, Vijay K Kuchroo
Type 1 regulatory T cells (Tr1 cells) are induced by interleukin-27 (IL-27) and have critical roles in the control of autoimmunity and resolution of inflammation. We found that the transcription factors IRF1 and BATF were induced early on after treatment with IL-27 and were required for the differentiation and function of Tr1 cells in vitro and in vivo. Epigenetic and transcriptional analyses revealed that both transcription factors influenced chromatin accessibility and expression of the genes required for Tr1 cell function...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#14
Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey, Jamie Rossjohn
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28323270/erratum-guidance-of-regulatory-t-cell-development-by-satb1-dependent-super-enhancer-establishment
#15
Yohko Kitagawa, Naganari Ohkura, Yujiro Kidani, Alexis Vandenbon, Keiji Hirota, Ryoji Kawakami, Keiko Yasuda, Daisuke Motooka, Shota Nakamura, Motonari Kondo, Ichiro Taniuchi, Terumi Kohwi-Shigematsu, Shimon Sakaguchi
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28323269/cd6-targeting
#16
Zoltan Fehervari
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28323268/ontogeny-and-homeostasis-of-cns-myeloid-cells
#17
REVIEW
Marco Prinz, Daniel Erny, Nora Hagemeyer
Myeloid cells in the central nervous system (CNS) represent a heterogeneous class of innate immune cells that contribute to the maintenance of tissue homeostasis differentially during development and adulthood. The subsets of CNS myeloid cells identified so far, including parenchymal microglia and non-parenchymal meningeal, perivascular and choroid-plexus macrophages, as well as disease-associated monocytes, have classically been distinguished on the basis of their surface epitope expression, localization and morphology...
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28323267/to-b-1-or-not-to-b-1
#18
Henry H Wortis
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28323266/themis-tery-is-solved
#19
David L Wiest
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28323265/adipose-tissue-ilcs
#20
Laurie A Dempsey
No abstract text is available yet for this article.
March 22, 2017: Nature Immunology
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