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Nature Immunology

Jinsung Hong, Chenghao Ge, Prithiviraj Jothikumar, Zhou Yuan, Baoyu Liu, Ke Bai, Kaitao Li, William Rittase, Miho Shinzawa, Yun Zhang, Amy Palin, Paul Love, Xinhua Yu, Khalid Salaita, Brian D Evavold, Alfred Singer, Cheng Zhu
The T cell antigen receptor (TCR) expressed on thymocytes interacts with self-peptide major histocompatibility complex (pMHC) ligands to signal apoptosis or survival. Here, we found that negative-selection ligands induced thymocytes to exert forces on the TCR and the co-receptor CD8 and formed cooperative TCR-pMHC-CD8 trimolecular 'catch bonds', whereas positive-selection ligands induced less sustained thymocyte forces on TCR and CD8 and formed shorter-lived, independent TCR-pMHC and pMHC-CD8 bimolecular 'slip bonds'...
November 12, 2018: Nature Immunology
Akinola Olumide Emmanuel, Stephen Arnovitz, Leila Haghi, Priya S Mathur, Soumi Mondal, Jasmin Quandt, Michael K Okoreeh, Mark Maienschein-Cline, Khashayarsha Khazaie, Marei Dose, Fotini Gounari
Thymocyte development requires a complex orchestration of multiple transcription factors. Ablating either TCF-1 or HEB in CD4+ CD8+ thymocytes elicits similar developmental outcomes including increased proliferation, decreased survival, and fewer late Tcra rearrangements. Here, we provide a mechanistic explanation for these similarities by showing that TCF-1 and HEB share ~7,000 DNA-binding sites genome wide and promote chromatin accessibility. The binding of both TCF-1 and HEB was required at these shared sites for epigenetic and transcriptional gene regulation...
November 12, 2018: Nature Immunology
Daisy Melandri, Iva Zlatareva, Raphaël A G Chaleil, Robin J Dart, Andrew Chancellor, Oliver Nussbaumer, Oxana Polyakova, Natalie A Roberts, Daniela Wesch, Dieter Kabelitz, Peter M Irving, Susan John, Salah Mansour, Paul A Bates, Pierre Vantourout, Adrian C Hayday
T lymphocytes expressing γδ T cell antigen receptors (TCRs) comprise evolutionarily conserved cells with paradoxical features. On the one hand, clonally expanded γδ T cells with unique specificities typify adaptive immunity. Conversely, large compartments of γδTCR+ intraepithelial lymphocytes (γδ IELs) exhibit limited TCR diversity and effect rapid, innate-like tissue surveillance. The development of several γδ IEL compartments depends on epithelial expression of genes encoding butyrophilin-like (Btnl (mouse) or BTNL (human)) members of the B7 superfamily of T cell co-stimulators...
November 12, 2018: Nature Immunology
Omer Dushek, Michael L Dustin
No abstract text is available yet for this article.
November 12, 2018: Nature Immunology
Xavier Michelet, Lydia Dyck, Andrew Hogan, Roisin M Loftus, Danielle Duquette, Kevin Wei, Semir Beyaz, Ali Tavakkoli, Cathriona Foley, Raymond Donnelly, Cliona O'Farrelly, Mathilde Raverdeau, Ashley Vernon, William Pettee, Donal O'Shea, Barbara S Nikolajczyk, Kingston H G Mills, Michael B Brenner, David Finlay, Lydia Lynch
Up to 49% of certain types of cancer are attributed to obesity, and potential mechanisms include overproduction of hormones, adipokines, and insulin. Cytotoxic immune cells, including natural killer (NK) cells and CD8+ T cells, are important in tumor surveillance, but little is known about the impact of obesity on immunosurveillance. Here, we show that obesity induces robust peroxisome proliferator-activated receptor (PPAR)-driven lipid accumulation in NK cells, causing complete 'paralysis' of their cellular metabolism and trafficking...
November 12, 2018: Nature Immunology
Christelle Harly, Thomas Ciucci
No abstract text is available yet for this article.
November 12, 2018: Nature Immunology
Hiroki Sekine, Masayuki Yamamoto, Hozumi Motohashi
No abstract text is available yet for this article.
November 5, 2018: Nature Immunology
Giovanni A M Povoleri, Estefania Nova-Lamperti, Cristiano Scottà, Giorgia Fanelli, Yun-Ching Chen, Pablo D Becker, Dominic Boardman, Benedetta Costantini, Marco Romano, Polychronis Pavlidis, Reuben McGregor, Eirini Pantazi, Daniel Chauss, Hong-Wei Sun, Han-Yu Shih, David J Cousins, Nichola Cooper, Nick Powell, Claudia Kemper, Mehdi Pirooznia, Arian Laurence, Shahram Kordasti, Majid Kazemian, Giovanna Lombardi, Behdad Afzali
Repair of tissue damaged during inflammatory processes is key to the return of local homeostasis and restoration of epithelial integrity. Here we describe CD161+ regulatory T (Treg ) cells as a distinct, highly suppressive population of Treg cells that mediate wound healing. These Treg cells were enriched in intestinal lamina propria, particularly in Crohn's disease. CD161+ Treg cells had an all-trans retinoic acid (ATRA)-regulated gene signature, and CD161 expression on Treg cells was induced by ATRA, which directly regulated the CD161 gene...
November 5, 2018: Nature Immunology
Darren J Perkins, Katharina Richard, Anne-Marie Hansen, Wendy Lai, Shreeram Nallar, Beverly Koller, Stefanie N Vogel
The unique cell biology of Toll-like receptor 4 (TLR4) allows it to initiate two signal-transduction cascades: a signal dependent on the adaptors TIRAP (Mal) and MyD88 that begins at the cell surface and regulates proinflammatory cytokines, and a signal dependent on the adaptors TRAM and TRIF that begins in the endosomes and drives the production of type I interferons. Negative feedback circuits to limit TLR4 signals from both locations are necessary to balance the inflammatory response. We describe a negative feedback loop driven by autocrine-paracrine prostaglandin E2 (PGE2 ) and the PGE2 receptor EP4 that restricted TRIF-dependent signals and the induction of interferon-β through the regulation of TLR4 trafficking...
November 5, 2018: Nature Immunology
Toszka Bohn, Steffen Rapp, Natascha Luther, Matthias Klein, Till-Julius Bruehl, Nobuhiko Kojima, Pamela Aranda Lopez, Jennifer Hahlbrock, Sabine Muth, Shogo Endo, Stefanie Pektor, Almut Brand, Kathrin Renner, Vanessa Popp, Katharina Gerlach, Dennis Vogel, Christina Lueckel, Danielle Arnold-Schild, Jacques Pouyssegur, Marina Kreutz, Magdalena Huber, Jochem Koenig, Benno Weigmann, Hans-Christian Probst, Esther von Stebut, Christian Becker, Hansjoerg Schild, Edgar Schmitt, Tobias Bopp
Many tumors evolve sophisticated strategies to evade the immune system, and these represent major obstacles for efficient antitumor immune responses. Here we explored a molecular mechanism of metabolic communication deployed by highly glycolytic tumors for immunoevasion. In contrast to colon adenocarcinomas, melanomas showed comparatively high glycolytic activity, which resulted in high acidification of the tumor microenvironment. This tumor acidosis induced Gprotein-coupled receptor-dependent expression of the transcriptional repressor ICER in tumor-associated macrophages that led to their functional polarization toward a non-inflammatory phenotype and promoted tumor growth...
November 5, 2018: Nature Immunology
Hiroyuki Hosokawa, Maile Romero-Wolf, Mary A Yui, Jonas Ungerbäck, Maria L G Quiloan, Masaki Matsumoto, Keiichi I Nakayama, Tomoaki Tanaka, Ellen V Rothenberg
Multipotent progenitor cells confirm their T cell-lineage identity in the CD4- CD8- double-negative (DN) pro-T cell DN2 stages, when expression of the essential transcription factor Bcl11b begins. In vivo and in vitro stage-specific deletions globally identified Bcl11b-controlled target genes in pro-T cells. Proteomics analysis revealed that Bcl11b associated with multiple cofactors and that its direct action was needed to recruit those cofactors to selective target sites. Regions near functionally regulated target genes showed enrichment for those sites of Bcl11b-dependent recruitment of cofactors, and deletion of individual cofactors relieved the repression of many genes normally repressed by Bcl11b...
October 30, 2018: Nature Immunology
Tomokazu Sumida, Matthew R Lincoln, Chinonso M Ukeje, Donald M Rodriguez, Hiroshi Akazawa, Tetsuo Noda, Atsuhiko T Naito, Issei Komuro, Margarita Dominguez-Villar, David A Hafler
Foxp3+ regulatory T cells (Treg cells) are the central component of peripheral immune tolerance. Whereas a dysregulated Treg cytokine signature has been observed in autoimmune diseases, the regulatory mechanisms underlying pro- and anti-inflammatory cytokine production are elusive. Here, we identify an imbalance between the cytokines IFN-γ and IL-10 as a shared Treg signature present in patients with multiple sclerosis and under high-salt conditions. RNA-sequencing analysis on human Treg subpopulations revealed β-catenin as a key regulator of IFN-γ and IL-10 expression...
October 29, 2018: Nature Immunology
Simon P Jochems, Fernando Marcon, Beatriz F Carniel, Mark Holloway, Elena Mitsi, Emma Smith, Jenna F Gritzfeld, Carla Solórzano, Jesús Reiné, Sherin Pojar, Elissavet Nikolaou, Esther L German, Angie Hyder-Wright, Helen Hill, Caz Hales, Wouter A A de Steenhuijsen Piters, Debby Bogaert, Hugh Adler, Seher Zaidi, Victoria Connor, Stephen B Gordon, Jamie Rylance, Helder I Nakaya, Daniela M Ferreira
Colonization of the upper respiratory tract by pneumococcus is important both as a determinant of disease and for transmission into the population. The immunological mechanisms that contain pneumococcus during colonization are well studied in mice but remain unclear in humans. Loss of this control of pneumococcus following infection with influenza virus is associated with secondary bacterial pneumonia. We used a human challenge model with type 6B pneumococcus to show that acquisition of pneumococcus induced early degranulation of resident neutrophils and recruitment of monocytes to the nose...
October 29, 2018: Nature Immunology
Benjamin Knier, Michael Hiltensperger, Christopher Sie, Lilian Aly, Gildas Lepennetier, Thomas Engleitner, Garima Garg, Andreas Muschaweckh, Meike Mitsdörffer, Uwe Koedel, Bastian Höchst, Percy Knolle, Matthias Gunzer, Bernhard Hemmer, Roland Rad, Doron Merkler, Thomas Korn
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) have been characterized in the context of malignancies. Here we show that PMN-MDSCs can restrain B cell accumulation during central nervous system (CNS) autoimmunity. Ly6G+ cells were recruited to the CNS during experimental autoimmune encephalomyelitis (EAE), interacted with B cells that produced the cytokines GM-CSF and interleukin-6 (IL-6), and acquired properties of PMN-MDSCs in the CNS in a manner dependent on the signal transducer STAT3. Depletion of Ly6G+ cells or dysfunction of Ly6G+ cells through conditional ablation of STAT3 led to the selective accumulation of GM-CSF-producing B cells in the CNS compartment, which in turn promoted an activated microglial phenotype and lack of recovery from EAE...
October 29, 2018: Nature Immunology
Takumi Maruhashi, Il-Mi Okazaki, Daisuke Sugiura, Suzuka Takahashi, Takeo K Maeda, Kenji Shimizu, Taku Okazaki
The success of tumor immunotherapy targeting the inhibitory co-receptors PD-1 and CTLA-4 has indicated that many other co-receptors might be potential druggable targets, despite limited information about their functional differences. Here we identified a unique target selectivity for the inhibitory co-receptor LAG-3 that was intrinsic to its immunoregulatory roles. Although LAG-3 has been reported to recognize major histocompatibility complex (MHC) class II, it did not recognize MHC class II universally; instead, we found that it selectively recognized stable complexes of peptide and MHC class II (pMHCII)...
October 22, 2018: Nature Immunology
Erica Ollmann Saphire, Sharon L Schendel, Bronwyn M Gunn, Jacob C Milligan, Galit Alter
Recent Ebola virus disease epidemics have highlighted the need for effective vaccines and therapeutics to prevent future outbreaks. Antibodies are clearly critical for control of this deadly disease; however, the specific mechanisms of action of protective antibodies have yet to be defined. In this Perspective we discuss the antibody features that correlate with in vivo protection during infection with Ebola virus, based on the results of a systematic and comprehensive study of antibodies directed against this virus...
October 17, 2018: Nature Immunology
(no author information available yet)
Better understanding of the biology of infectious agents and of the mechanisms of efficient immune responses advances strategies to achieve protection against infectious diseases.
October 17, 2018: Nature Immunology
Fu Sheng Wang, Linqi Zhang, Daniel Douek, Andrew McMichael, Xiao-Ning Xu, Sharon R Lewin
No abstract text is available yet for this article.
October 17, 2018: Nature Immunology
Ian A Cockburn, Robert A Seder
Development of a malaria vaccine remains a critical priority to decrease clinical disease and mortality and facilitate eradication. Accordingly, RTS,S, a protein-subunit vaccine, has completed phase III clinical trials and confers ~30% protection against clinical infection over 4 years. Whole-attenuated-sporozoite and viral-subunit vaccines induce between 20% and 100% protection against controlled human malaria infection, but there is limited published evidence to date for durable, high-level efficacy (>50%) against natural exposure...
October 17, 2018: Nature Immunology
Laurie A Dempsey
No abstract text is available yet for this article.
October 17, 2018: Nature Immunology
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