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Nature Immunology

Steven J Van Dyken, Jesse C Nussbaum, Jinwoo Lee, Ari B Molofsky, Hong-Erh Liang, Joshua L Pollack, Rachel E Gate, Genevieve E Haliburton, Chun J Ye, Alexander Marson, David J Erle, Richard M Locksley
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 mediated by exposure to the tissue-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP). Loss of these three tissue signals did not affect lymph node priming, but abrogated the terminal differentiation of effector TH2 cells and adaptive lung inflammation in a T cell-intrinsic manner...
October 17, 2016: Nature Immunology
Sabrina Torre, Maria J Polyak, David Langlais, Nassima Fodil, James M Kennedy, Irena Radovanovic, Joanne Berghout, Gabriel A Leiva-Torres, Connie M Krawczyk, Subburaj Ilangumaran, Karen Mossman, Chen Liang, Klaus-Peter Knobeloch, Luke M Healy, Jack Antel, Nathalie Arbour, Alexandre Prat, Jacek Majewski, Mark Lathrop, Silvia M Vidal, Philippe Gros
Genes and pathways in which inactivation dampens tissue inflammation present new opportunities for understanding the pathogenesis of common human inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. We identified a mutation in the gene encoding the deubiquitination enzyme USP15 (Usp15(L749R)) that protected mice against both experimental cerebral malaria (ECM) induced by Plasmodium berghei and experimental autoimmune encephalomyelitis (EAE). Combining immunophenotyping and RNA sequencing in brain (ECM) and spinal cord (EAE) revealed that Usp15(L749R)-associated resistance to neuroinflammation was linked to dampened type I interferon responses in situ...
October 10, 2016: Nature Immunology
Valerie A Gerriets, Rigel J Kishton, Marc O Johnson, Sivan Cohen, Peter J Siska, Amanda G Nichols, Marc O Warmoes, Aguirre A de Cubas, Nancie J MacIver, Jason W Locasale, Laurence A Turka, Andrew D Wells, Jeffrey C Rathmell
CD4(+) effector T cells (Teff cells) and regulatory T cells (Treg cells) undergo metabolic reprogramming to support proliferation and immunological function. Although signaling via the lipid kinase PI(3)K (phosphatidylinositol-3-OH kinase), the serine-threonine kinase Akt and the metabolic checkpoint kinase complex mTORC1 induces both expression of the glucose transporter Glut1 and aerobic glycolysis for Teff cell proliferation and inflammatory function, the mechanisms that regulate Treg cell metabolism and function remain unclear...
October 3, 2016: Nature Immunology
Peter T Sage, Noga Ron-Harel, Vikram R Juneja, Debattama R Sen, Seth Maleri, Waradon Sungnak, Vijay K Kuchroo, W Nicholas Haining, Nicolas Chevrier, Marcia Haigis, Arlene H Sharpe
Follicular regulatory T cells (TFR cells) inhibit follicular helper T cell (TFH cell)-mediated antibody production. The mechanisms by which TFR cells exert their key immunoregulatory functions are largely unknown. Here we found that TFR cells induced a distinct suppressive state in TFH cells and B cells, in which effector transcriptional signatures were maintained but key effector molecules and metabolic pathways were suppressed. The suppression of B cell antibody production and metabolism by TFR cells was durable and persisted even in the absence of TFR cells...
October 3, 2016: Nature Immunology
Junji Xing, Leiyun Weng, Bin Yuan, Zhuo Wang, Li Jia, Rui Jin, Hongbo Lu, Xian Chang Li, Yong-Jun Liu, Zhiqiang Zhang
The respiratory tract is heavily populated with innate immune cells, but the mechanisms that control such cells are poorly defined. Here we found that the E3 ubiquitin ligase TRIM29 was a selective regulator of the activation of alveolar macrophages, the expression of type I interferons and the production of proinflammatory cytokines in the lungs. We found that deletion of TRIM29 enhanced macrophage production of type I interferons and protected mice from infection with influenza virus, while challenge of Trim29(-/-) mice with Haemophilus influenzae resulted in lethal lung inflammation due to massive production of proinflammatory cytokines by macrophages...
October 3, 2016: Nature Immunology
Tiago C Luis, Sidinh Luc, Takuo Mizukami, Hanane Boukarabila, Supat Thongjuea, Petter S Woll, Emanuele Azzoni, Alice Giustacchini, Michael Lutteropp, Tiphaine Bouriez-Jones, Harsh Vaidya, Adam J Mead, Deborah Atkinson, Charlotta Böiers, Joana Carrelha, Iain C Macaulay, Roger Patient, Frederic Geissmann, Claus Nerlov, Rickard Sandberg, Marella F T R de Bruijn, C Clare Blackburn, Isabelle Godin, Sten Eirik W Jacobsen
The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors...
October 3, 2016: Nature Immunology
Motoko Y Kimura, Julien Thomas, Xuguang Tai, Terry I Guinter, Miho Shinzawa, Ruth Etzensperger, Zhenhu Li, Paul Love, Toshinori Nakayama, Alfred Singer
Major histocompatibility complex class I (MHC I) positive selection of CD8(+) T cells in the thymus requires that T cell antigen receptor (TCR) signaling end in time for cytokines to induce Runx3d, the CD8-lineage transcription factor. We examined the time required for these events and found that the overall duration of positive selection was similar for all CD8(+) thymocytes in mice, despite markedly different TCR signaling times. Notably, prolonged TCR signaling times were counter-balanced by accelerated Runx3d induction by cytokines and accelerated differentiation into CD8(+) T cells...
September 26, 2016: Nature Immunology
Mark Roufaiel, Eric Gracey, Allan Siu, Su-Ning Zhu, Andrew Lau, Hisham Ibrahim, Marwan Althagafi, Kelly Tai, Sharon J Hyduk, Kateryna O Cybulsky, Sherine Ensan, Angela Li, Rickvinder Besla, Henry M Becker, Haiyan Xiao, Sanjiv A Luther, Robert D Inman, Clinton S Robbins, Jenny Jongstra-Bilen, Myron I Cybulsky
Regions of the normal arterial intima predisposed to atherosclerosis are sites of ongoing monocyte trafficking and also contain resident myeloid cells with features of dendritic cells. However, the pathophysiological roles of these cells are poorly understood. Here we found that intimal myeloid cells underwent reverse transendothelial migration (RTM) into the arterial circulation after systemic stimulation of pattern-recognition receptors (PRRs). This process was dependent on expression of the chemokine receptor CCR7 and its ligand CCL19 by intimal myeloid cells...
September 26, 2016: Nature Immunology
Hui-Fern Koay, Nicholas A Gherardin, Anselm Enders, Liyen Loh, Laura K Mackay, Catarina F Almeida, Brendan E Russ, Claudia A Nold-Petry, Marcel F Nold, Sammy Bedoui, Zhenjun Chen, Alexandra J Corbett, Sidonia B G Eckle, Bronwyn Meehan, Yves d'Udekem, Igor E Konstantinov, Martha Lappas, Ligong Liu, Chris C Goodnow, David P Fairlie, Jamie Rossjohn, Mark M Chong, Katherine Kedzierska, Stuart P Berzins, Gabrielle T Belz, James McCluskey, Adam P Uldrich, Dale I Godfrey, Daniel G Pellicci
Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization...
September 26, 2016: Nature Immunology
Bryan King, Francesco Boccalatte, Kelly Moran-Crusio, Elmar Wolf, Jingjing Wang, Clarisse Kayembe, Charalampos Lazaris, Xiaofeng Yu, Beatriz Aranda-Orgilles, Anna Lasorella, Iannis Aifantis
Hematopoietic stem cells (HSCs) are dormant in the bone marrow and can be activated in response to diverse stresses to replenish all blood cell types. We identified the ubiquitin ligase Huwe1 as a crucial regulator of HSC function via its post-translational control of the oncoprotein N-myc (encoded by Mycn). We found Huwe1 to be essential for HSC self-renewal, quiescence and lymphoid-fate specification in mice. Through the use of a fluorescent fusion allele (Mycn(M)), we observed that N-myc expression was restricted to the most immature, multipotent stem and progenitor populations...
September 26, 2016: Nature Immunology
Frédéric Vély, Vincent Barlogis, Blandine Vallentin, Bénédicte Neven, Christelle Piperoglou, Thibaut Perchet, Maxime Petit, Nadia Yessaad, Fabien Touzot, Julie Bruneau, Nizar Mahlaoui, Nicolas Zucchini, Catherine Farnarier, Gérard Michel, Despina Moshous, Stéphane Blanche, Arnaud Dujardin, Hergen Spits, Jörg H W Distler, Andreas Ramming, Capucine Picard, Rachel Golub, Alain Fischer, Eric Vivier
Innate lymphoid cells (ILCs) have potent immunological functions in experimental conditions in mice, but their contributions to immunity in natural conditions in humans have remained unclear. We investigated the presence of ILCs in a cohort of patients with severe combined immunodeficiency (SCID). All ILC subsets were absent in patients with SCID who had mutation of the gene encoding the common γ-chain cytokine receptor subunit IL-2Rγ or the gene encoding the tyrosine kinase JAK3. T cell reconstitution was observed in patients with SCID after hematopoietic stem cell transplantation (HSCT), but the patients still had considerably fewer ILCs in the absence of myeloablation than did healthy control subjects, with the exception of rare cases of reconstitution of the ILC1 subset of ILCs...
September 12, 2016: Nature Immunology
Xianli Shen, Miguel A Burguillos, Ahmed M Osman, Jeroen Frijhoff, Alejandro Carrillo-Jiménez, Sachie Kanatani, Martin Augsten, Dalel Saidi, Johanna Rodhe, Edel Kavanagh, Anthony Rongvaux, Vilma Rraklli, Ulrika Nyman, Johan Holmberg, Arne Östman, Richard A Flavell, Antonio Barragan, Jose Luis Venero, Klas Blomgren, Bertrand Joseph
Glioma cells recruit and exploit microglia (the resident immune cells of the brain) for their proliferation and invasion ability. The underlying molecular mechanism used by glioma cells to transform microglia into a tumor-supporting phenotype has remained elusive. We found that glioma-induced microglia conversion was coupled to a reduction in the basal activity of microglial caspase-3 and increased S-nitrosylation of mitochondria-associated caspase-3 through inhibition of thioredoxin-2 activity, and that inhibition of caspase-3 regulated microglial tumor-supporting function...
September 12, 2016: Nature Immunology
Takatoshi Chinen, Arun K Kannan, Andrew G Levine, Xiying Fan, Ulf Klein, Ye Zheng, Georg Gasteiger, Yongqiang Feng, Jason D Fontenot, Alexander Y Rudensky
Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells...
September 5, 2016: Nature Immunology
Richard Beatson, Virginia Tajadura-Ortega, Daniela Achkova, Gianfranco Picco, Theodora-Dorita Tsourouktsoglou, Sandra Klausing, Matthew Hillier, John Maher, Thomas Noll, Paul R Crocker, Joyce Taylor-Papadimitriou, Joy M Burchell
Siglec-9 is a sialic-acid-binding lectin expressed predominantly on myeloid cells. Aberrant glycosylation occurs in essentially all types of cancers and results in increased sialylation. Thus, when the mucin MUC1 is expressed on cancer cells, it is decorated by multiple short, sialylated O-linked glycans (MUC1-ST). Here we found that this cancer-specific MUC1 glycoform, through engagement of Siglec-9, 'educated' myeloid cells to release factors associated with determination of the tumor microenvironment and disease progression...
September 5, 2016: Nature Immunology
Eun-Young Lee, Hyun-Cheol Lee, Hyun-Kwan Kim, Song Yee Jang, Seong-Jun Park, Yong-Hoon Kim, Jong Hwan Kim, Jungwon Hwang, Jae-Hoon Kim, Tae-Hwan Kim, Abul Arif, Seon-Young Kim, Young-Ki Choi, Cheolju Lee, Chul-Ho Lee, Jae U Jung, Paul L Fox, Sunghoon Kim, Jong-Soo Lee, Myung Hee Kim
The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity...
September 5, 2016: Nature Immunology
Ioana Visan
No abstract text is available yet for this article.
October 19, 2016: Nature Immunology
Laurie A Dempsey
No abstract text is available yet for this article.
October 19, 2016: Nature Immunology
Korneel Grauwet, E Antonio Chiocca
No abstract text is available yet for this article.
October 19, 2016: Nature Immunology
Haiguang Wang, Kristin A Hogquist
No abstract text is available yet for this article.
October 19, 2016: Nature Immunology
Laurie A Dempsey
No abstract text is available yet for this article.
October 19, 2016: Nature Immunology
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