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Science Immunology

Conor J Kearney, Stephin J Vervoort, Simon J Hogg, Kelly M Ramsbottom, Andrew J Freeman, Najoua Lalaoui, Lizzy Pijpers, Jessica Michie, Kristin K Brown, Deborah A Knight, Vivien Sutton, Paul A Beavis, Ilia Voskoboinik, Phil K Darcy, John Silke, Joseph A Trapani, Ricky W Johnstone, Jane Oliaro
Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a series of whole-genome clustered regularly interspaced short palindromic repeat (CRISPR)-based screens performed in vitro and in vivo to identify mechanisms of tumor immune evasion from cytotoxic lymphocytes [CD8+ T cells and natural killer (NK) cells]. Deletion of key genes within the tumor necrosis factor (TNF) signaling, interferon-γ (IFN-γ) signaling, and antigen presentation pathways provided protection of tumor cells from CD8+ T cell-mediated killing and blunted antitumor immune responses in vivo...
May 18, 2018: Science Immunology
Fanny Tzelepis, Julianna Blagih, Nargis Khan, Joshua Gillard, Laura Mendonca, Dominic G Roy, Eric H Ma, Philippe Joubert, Russell G Jones, Maziar Divangahi
Mycobacterium tuberculosis ( Mtb ) is one of the most ancient human pathogens, yet the exact mechanism(s) of host defense against Mtb remains unclear. Although one-third of the world's population is chronically infected with Mtb , only 5 to 10% develop active disease. This indicates that, in addition to resistance mechanisms that control bacterial burden, the host has also evolved strategies to tolerate the presence of Mtb to limit disease severity. We identify mitochondrial cyclophilin D (CypD) as a critical checkpoint of T cell metabolism that controls the expansion of activated T cells...
May 11, 2018: Science Immunology
Lokesh A Kalekar, Michael D Rosenblum
IL-25 from keratinocytes mediates skin inflammation in psoriasis.
May 4, 2018: Science Immunology
Sarah E Henrickson
A human antibody that prevents EBV infection is identified by studying memory B cells that recognize core EBV fusion proteins.
May 4, 2018: Science Immunology
Andrew J Macpherson, Bahtiyar Yilmaz
Perturbations in gut microbiota of IgA-deficient humans provide insight into how secretory IgA shapes microbiota composition.
May 4, 2018: Science Immunology
Nina Schmolka, Pedro H Papotto, Paula Vargas Romero, Tiago Amado, Francisco J Enguita, Ana Amorim, Ana F Rodrigues, Katrina E Gordon, Ana S Coroadinha, Mark Boldin, Karine Serre, Amy H Buck, Anita Q Gomes, Bruno Silva-Santos
γδ T cells are major providers of proinflammatory cytokines. They are preprogrammed in the mouse thymus into distinct subsets producing either interleukin-17 (IL-17) or interferon-γ (IFN-γ), which segregate with CD27 expression. In the periphery, CD27- γδ (γδ27- ) T cells can be induced under inflammatory conditions to coexpress IL-17 and IFN-γ; the molecular basis of this functional plasticity remains to be determined. On the basis of differential microRNA (miRNA) expression analysis and modulation in γδ T cell subsets, we identified miR-146a as a thymically imprinted post-transcriptional brake to limit IFN-γ expression in γδ27- T cells in vitro and in vivo...
May 4, 2018: Science Immunology
Erin C Zook, Zhong-Yin Li, Yiying Xu, Renée F de Pooter, Mihalis Verykokakis, Aimee Beaulieu, Anna Lasorella, Mark Maienschein-Cline, Joseph C Sun, Mikael Sigvardsson, Barbara L Kee
All innate lymphoid cells (ILCs) require the small helix-loop-helix transcription factor ID2, but the functions of ID2 are not well understood in these cells. We show that mature natural killer (NK) cells, the prototypic ILCs, developed in mice lacking ID2 but remained as precursor CD27+ CD11b- cells that failed to differentiate into CD27- CD11b+ cytotoxic effectors. We show that ID2 limited chromatin accessibility at E protein binding sites near naïve T lymphocyte-associated genes including multiple chemokine receptors, cytokine receptors, and signaling molecules and altered the NK cell response to inflammatory cytokines...
April 27, 2018: Science Immunology
Teresita L Arenzana, Steve Lianoglou, Akiko Seki, Celine Eidenschenk, Tommy Cheung, Dhaya Seshasayee, Thijs Hagenbeek, Arivazhagan Sambandam, Rajkumar Noubade, Ivan Peng, Justin Lesch, Jason DeVoss, Xiumin Wu, Wyne P Lee, Patrick Caplazi, Joshua Webster, Jinfeng Liu, Victoria C Pham, David Arnott, Jennie R Lill, Zora Modrusan, Anwesha Dey, Sascha Rutz
Loss of function of the nuclear deubiquitinating enzyme BRCA1-associated protein-1 (BAP1) is associated with a wide spectrum of cancers. We report that tamoxifen-induced BAP1 deletion in adult mice resulted in severe thymic atrophy. BAP1 was critical for T cell development at several stages. In the thymus, BAP1 was required for progression through the pre-T cell receptor checkpoint. Peripheral T cells lacking BAP1 demonstrated a defect in homeostatic and antigen-driven expansion. Deletion of BAP1 resulted in suppression of E2F target genes and defects in cell cycle progression, which was dependent on the catalytic activity of BAP1, but did not require its interaction with host cell factor-1 (HCF-1)...
April 20, 2018: Science Immunology
Héloïse Beutier, Béatrice Hechler, Ophélie Godon, Yu Wang, Caitlin M Gillis, Luc de Chaisemartin, Aurélie Gouel-Chéron, Stéphanie Magnenat, Lynn E Macdonald, Andrew J Murphy, Sylvie Chollet-Martin, Dan Longrois, Christian Gachet, Pierre Bruhns, Friederike Jönsson
Platelets are key regulators of vascular integrity; however, their role in anaphylaxis, a life-threatening systemic allergic reaction characterized by the loss of vascular integrity and vascular leakage, remains unknown. Anaphylaxis is a consequence of inappropriate cellular responses triggered by antibodies to generally harmless antigens, resulting in a massive mediator release and rapidly occurring organ dysfunction. Human platelets express receptors for immunoglobulin G (IgG) antibodies and can release potent mediators, yet their contribution to anaphylaxis has not been previously addressed in mouse models, probably because mice do not express IgG receptors on platelets...
April 13, 2018: Science Immunology
Ira Surolia, Shiv Pillai
Engineered cytokines are able to improve immunotherapy in mouse tumor models.
April 6, 2018: Science Immunology
Rachael A Clark
T follicular helper-like cells and IL-21 are drivers of skin fibrosis in systemic sclerosis.
April 6, 2018: Science Immunology
Ifor R Williams
Charting new horizons for Science Immunology .
April 6, 2018: Science Immunology
Ben S Wendel, Daniel Del Alcazar, Chenfeng He, Perla M Del Río-Estrada, Benjamas Aiamkitsumrit, Yuria Ablanedo-Terrazas, Stefany M Hernandez, Ke-Yue Ma, Michael R Betts, Laura Pulido, Jun Huang, Phyllis A Gimotty, Gustavo Reyes-Terán, Ning Jiang, Laura F Su
Follicular helper CD4+ T cells (TFH ) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH cell frequencies are increased in lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether HIV inhibits TFH responses in LNs remains unclear. Advances in this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry with T cell receptor repertoire sequencing to interrogate the composition of TFH cells in primary human LNs...
April 6, 2018: Science Immunology
Carmelo Carmona-Rivera, Kevin L Bicker, Paul R Thompson, Jane H Buckner, William H Robinson, David A Fox, Mariana J Kaplan
The citrullinome cargo in neutrophil extracellular traps varies according to disease condition and stimulation conditions.
March 30, 2018: Science Immunology
Jing Shi, Felipe Andrade
Discrepancies on the role of citrullination in the induction of experimental arthritis by neutrophils extracellular traps.
March 30, 2018: Science Immunology
Gustaf Christoffersson, Grzegorz Chodaczek, Sowbarnika S Ratliff, Ken Coppieters, Matthias G von Herrath
The inflammatory lesion at the pancreatic islet in type 1 diabetes (T1D) contains a heterogeneous infiltrate of T cells. In human and mouse studies, a large majority (98 to 99%) of the cytotoxic CD8+ T cells (CTLs) within islets are not specific to any islet antigen and are thought to passively add to tissue damage. We show by intravital confocal microscopy the opposite, immune-regulatory function of this cohort of CTLs. Diabetes did not develop in mice with islets showing high levels of infiltration of non-islet-specific CTLs not recognizing local antigens...
March 23, 2018: Science Immunology
Ariel Molly Wilson, Zhuo Shao, Vanessa Grenier, Gaëlle Mawambo, Jean-François Daudelin, Agnieszka Dejda, Frédérique Pilon, Natalija Popovic, Salix Boulet, Célia Parinot, Malika Oubaha, Nathalie Labrecque, Vincent de Guire, Mathieu Laplante, Guillaume Lettre, Florian Sennlaub, Jean-Sebastien Joyal, Michel Meunier, Przemyslaw Sapieha
Obesity gives rise to metabolic complications by mechanisms that are poorly understood. Although chronic inflammatory signaling in adipose tissue is typically associated with metabolic deficiencies linked to excessive weight gain, we identified a subset of neuropilin-1 (NRP1)-expressing myeloid cells that accumulate in adipose tissue and protect against obesity and metabolic syndrome. Ablation of NRP1 in macrophages compromised lipid uptake in these cells, which reduced substrates for fatty acid β-oxidation and shifted energy metabolism of these macrophages toward a more inflammatory glycolytic metabolism...
March 16, 2018: Science Immunology
Stanislav O Fedechkin, Natasha L George, Jacob T Wolff, Lawrence M Kauvar, Rebecca M DuBois
Respiratory syncytial virus (RSV) is a top cause of severe lower respiratory tract disease and mortality in young children and the elderly. The viral envelope G glycoprotein contributes to pathogenesis through its roles in host cell attachment and modulation of host immunity. Although the G glycoprotein is a target of protective RSV-neutralizing antibodies, its development as a vaccine antigen has been hindered by its heterogeneous glycosylation and sequence variability outside a conserved central domain (CCD)...
March 9, 2018: Science Immunology
Gabriel K Griffin
A subset of canonical "interferon-stimulated" antiviral genes are intrinsically expressed in and protect mammalian stem cells.
March 2, 2018: Science Immunology
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