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Science Immunology

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https://www.readbyqxmd.com/read/30006464/mr1-displays-the-microbial-metabolome-driving-selective-mr1-restricted-t-cell-receptor-usage
#1
Melanie J Harriff, Curtis McMurtrey, Cara A Froyd, Haihong Jin, Meghan Cansler, Megan Null, Aneta Worley, Erin W Meermeier, Gwendolyn Swarbrick, Aaron Nilsen, Deborah A Lewinsohn, William Hildebrand, Erin J Adams, David M Lewinsohn
MR1-restricted T cells (MR1Ts) are a T cell subset that recognize and mediate host defense to a broad array of microbial pathogens, including respiratory pathogens (e.g., Mycobacterium tuberculosis , Streptococcus pyogenes , and Francisella tularensis ) and enteric pathogens (e.g., Escherichia coli and Salmonella species). Mucosal-associated invariant T (MAIT) cells, a subset of MR1Ts, were historically defined by the use of a semi-invariant T cell receptor (TCR) and recognition of small molecules derived from the riboflavin biosynthesis pathway presented on MR1...
July 13, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980623/cross-presentation-in-pdcs-an-energetic-m-cat-and-mouse-game
#2
Sunil Joshi, Asha Pillai
pDC cross-presentation of antigens to CD8+ T cells depends on mitochondrial generation of reactive oxygen species.
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980622/macrophages-that-fix-or-break-the-heart
#3
Andrew Lichtman
Human myocardium contains different types of macrophages with heterogenous functions and origins.
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980621/celebrating-twoness-at-science-immunology
#4
EDITORIAL
Ifor R Williams
Science Immunology 's second anniversary invites a pause for editorial reflections.
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980620/if-we-build-it-they-will-come
#5
EDITORIAL
Anand Balasubramani
Our author-centric approach to publishing your research.
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980619/type-2-immunity-expanding-our-view
#6
REVIEW
Clare M Lloyd, Robert J Snelgrove
The classical vision of type 2 immune reactions is that they are characterized by a distinct cellular and cytokine repertoire that is critical for host resistance against helminthic worm infections but, when dysregulated, may cause atopic reactions that result in conditions such as asthma, rhinitis, dermatitis, and anaphylaxis. In this traditional view, the type 2 response is categorized as an adaptive immune response with differentiated T helper cells taking center stage, driving eosinophil recruitment and immunoglobulin production via the secretion of a distinct repertoire of cytokines that include interleukin-4 (IL-4), IL-5, and IL-13...
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980618/revisiting-il-2-biology-and-therapeutic-prospects
#7
REVIEW
Abul K Abbas, Eleonora Trotta, Dimitre R Simeonov, Alexander Marson, Jeffrey A Bluestone
Interleukin-2 (IL-2), the first cytokine that was molecularly cloned, was shown to be a T cell growth factor essential for the proliferation of T cells and the generation of effector and memory cells. On the basis of this activity, the earliest therapeutic application of IL-2 was to boost immune responses in cancer patients. Therefore, it was a surprise that genetic deletion of the cytokine or its receptor led not only to the expected immune deficiency but also to systemic autoimmunity and lymphoproliferation...
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29980617/metabolic-signaling-directs-the-reciprocal-lineage-decisions-of-%C3%AE-%C3%AE-and-%C3%AE-%C3%AE-t-cells
#8
Kai Yang, Daniel Bastardo Blanco, Xiang Chen, Pradyot Dash, Geoffrey Neale, Celeste Rosencrance, John Easton, Wenan Chen, Changde Cheng, Yogesh Dhungana, Anil Kc, Walid Awad, Xi-Zhi J Guo, Paul G Thomas, Hongbo Chi
The interaction between extrinsic factors and intrinsic signal strength governs thymocyte development, but the mechanisms linking them remain elusive. We report that mechanistic target of rapamycin complex 1 (mTORC1) couples microenvironmental cues with metabolic programs to orchestrate the reciprocal development of two fundamentally distinct T cell lineages, the αβ and γδ T cells. Developing thymocytes dynamically engage metabolic programs including glycolysis and oxidative phosphorylation, as well as mTORC1 signaling...
July 6, 2018: Science Immunology
https://www.readbyqxmd.com/read/29934344/mitochondria-maintain-controlled-activation-state-of-epithelial-resident-t-lymphocytes
#9
Špela Konjar, Ulrika C Frising, Cristina Ferreira, Reinhard Hinterleitner, Toufic Mayassi, Qifeng Zhang, Birte Blankenhaus, Nejc Haberman, Yunhua Loo, Joana Guedes, Marta Baptista, Silvia Innocentin, Joerg Stange, Douglas Strathdee, Bana Jabri, Marc Veldhoen
Epithelial-resident T lymphocytes, such as intraepithelial lymphocytes (IELs) located at the intestinal barrier, can offer swift protection against invading pathogens. Lymphocyte activation is strictly regulated because of its potential harmful nature and metabolic cost, and most lymphocytes are maintained in a quiescent state. However, IELs are kept in a heightened state of activation resembling effector T cells but without cytokine production or clonal proliferation. We show that this controlled activation state correlates with alterations in the IEL mitochondrial membrane, especially the cardiolipin composition...
June 22, 2018: Science Immunology
https://www.readbyqxmd.com/read/29907692/who-regulates-whom-znf341-is-an-additional-player-in-the-stat3-t-h-17-song
#10
REVIEW
Avery August
Deficiency of ZNF341, a transcription factor featuring 12 Cys2His2 zinc fingers that regulates the expression and autoinduction of STAT3 (signal transducer and activator of transcription 3), results in hyper-immunoglobulin E syndrome and defective T helper 17 cell differentiation in humans.
June 15, 2018: Science Immunology
https://www.readbyqxmd.com/read/29907691/a-recessive-form-of-hyper-ige-syndrome-by-disruption-of-znf341-dependent-stat3-transcription-and-activity
#11
Vivien Béziat, Juan Li, Jian-Xin Lin, Cindy S Ma, Peng Li, Aziz Bousfiha, Isabelle Pellier, Samaneh Zoghi, Safa Baris, Sevgi Keles, Paul Gray, Ning Du, Yi Wang, Yoann Zerbib, Romain Lévy, Thibaut Leclercq, Frédégonde About, Ai Ing Lim, Geetha Rao, Kathryn Payne, Simon J Pelham, Danielle T Avery, Elissa K Deenick, Bethany Pillay, Janet Chou, Romain Guery, Aziz Belkadi, Antoine Guérin, Mélanie Migaud, Vimel Rattina, Fatima Ailal, Ibtihal Benhsaien, Matthieu Bouaziz, Tanwir Habib, Damien Chaussabel, Nico Marr, Jamel El-Benna, Bodo Grimbacher, Orli Wargon, Jacinta Bustamante, Bertrand Boisson, Ingrid Müller-Fleckenstein, Bernhard Fleckenstein, Marie-Olivia Chandesris, Matthias Titeux, Sylvie Fraitag, Marie-Alexandra Alyanakian, Marianne Leruez-Ville, Capucine Picard, Isabelle Meyts, James P Di Santo, Alain Hovnanian, Ayper Somer, Ahmet Ozen, Nima Rezaei, Talal A Chatila, Laurent Abel, Warren J Leonard, Stuart G Tangye, Anne Puel, Jean-Laurent Casanova
Heterozygosity for human signal transducer and activator of transcription 3 ( STAT3 ) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein...
June 15, 2018: Science Immunology
https://www.readbyqxmd.com/read/29907690/znf341-controls-stat3-expression-and-thereby-immunocompetence
#12
Stefanie Frey-Jakobs, Julia M Hartberger, Manfred Fliegauf, Claudia Bossen, Magdalena L Wehmeyer, Johanna C Neubauer, Alla Bulashevska, Michele Proietti, Philipp Fröbel, Christina Nöltner, Linlin Yang, Jessica Rojas-Restrepo, Niko Langer, Sandra Winzer, Karin R Engelhardt, Cristina Glocker, Dietmar Pfeifer, Adi Klein, Alejandro A Schäffer, Irina Lagovsky, Idit Lachover-Roth, Vivien Béziat, Anne Puel, Jean-Laurent Casanova, Bernhard Fleckenstein, Stephan Weidinger, Sara S Kilic, Ben-Zion Garty, Amos Etzioni, Bodo Grimbacher
Signal transducer and activator of transcription 3 (STAT3) is a central regulator of immune homeostasis. STAT3 levels are strictly controlled, and STAT3 impairment contributes to several diseases including the monogenic autosomal-dominant hyper-immunoglobulin E (IgE) syndrome (AD-HIES). We investigated patients of four consanguineous families with an autosomal-recessive disorder resembling the phenotype of AD-HIES, with symptoms of immunodeficiency, recurrent infections, skeletal abnormalities, and elevated IgE...
June 15, 2018: Science Immunology
https://www.readbyqxmd.com/read/29884618/cd4-t-cell-mediated-hla-class-ii-cross-restriction-in-hiv-controllers
#13
Moran Galperin, Carine Farenc, Madhura Mukhopadhyay, Dhilshan Jayasinghe, Amandine Decroos, Daniela Benati, Li Lynn Tan, Lisa Ciacchi, Hugh H Reid, Jamie Rossjohn, Lisa A Chakrabarti, Stephanie Gras
Rare individuals, termed HIV controllers, spontaneously control HIV infection by mounting efficient T cell responses against the virus. Protective CD4+ T cell responses from HIV controllers involve high-affinity public T cell receptors (TCRs) recognizing an immunodominant capsid epitope (Gag293) presented by a remarkably broad array of human leukocyte antigen (HLA) class II molecules. Here, we determine the structures of a prototypical public TCR bound to HLA-DR1, HLA-DR11, and HLA-DR15 molecules presenting the Gag293 epitope...
June 8, 2018: Science Immunology
https://www.readbyqxmd.com/read/29858289/bats-are-blind-to-the-deadly-effects-of-viruses
#14
Kevin C O'Connor
Bats that harbor lethal viruses avoid disease through an evolved antiviral defense strategy that leverages tolerance for infections.
June 1, 2018: Science Immunology
https://www.readbyqxmd.com/read/29858288/bigger-and-better-in-tex-s
#15
Sunil Joshi, Asha Pillai
High-dimensional profiling defines novel metrics of T cell exhaustion in HIV and cancer.
June 1, 2018: Science Immunology
https://www.readbyqxmd.com/read/29858287/resident-t-cells-stand-up-to-hiv
#16
REVIEW
Nadia R Roan
HIV-specific resident memory T cells are abundant in lymphoid tissues of elite controllers and exhibit distinct functional properties.
June 1, 2018: Science Immunology
https://www.readbyqxmd.com/read/29858286/identification-and-characterization-of-hiv-specific-resident-memory-cd8-t-cells-in-human-lymphoid-tissue
#17
Marcus Buggert, Son Nguyen, Gonzalo Salgado-Montes de Oca, Bertram Bengsch, Samuel Darko, Amy Ransier, Emily R Roberts, Daniel Del Alcazar, Irene Bukh Brody, Laura A Vella, Lalit Beura, Sathi Wijeyesinghe, Ramin S Herati, Perla M Del Rio Estrada, Yuria Ablanedo-Terrazas, Leticia Kuri-Cervantes, Alberto Sada Japp, Sasikanth Manne, Shant Vartanian, Austin Huffman, Johan K Sandberg, Emma Gostick, Gregory Nadolski, Guido Silvestri, David H Canaday, David A Price, Constantinos Petrovas, Laura F Su, Golnaz Vahedi, Yoav Dori, Ian Frank, Maxim G Itkin, E John Wherry, Steven G Deeks, Ali Naji, Gustavo Reyes-Terán, David Masopust, Daniel C Douek, Michael R Betts
Current paradigms of CD8+ T cell-mediated protection in HIV infection center almost exclusively on studies of peripheral blood, which is thought to provide a window into immune activity at the predominant sites of viral replication in lymphoid tissues (LTs). Through extensive comparison of blood, thoracic duct lymph (TDL), and LTs in different species, we show that many LT memory CD8+ T cells bear phenotypic, transcriptional, and epigenetic signatures of resident memory T cells (TRMs ). Unlike their circulating counterparts in blood or TDL, most of the total and follicular HIV-specific CD8+ T cells in LTs also resemble TRMs Moreover, high frequencies of HIV-specific CD8+ TRMs with skewed clonotypic profiles relative to matched blood samples are present in LTs of individuals who spontaneously control HIV replication in the absence of antiretroviral therapy (elite controllers)...
June 1, 2018: Science Immunology
https://www.readbyqxmd.com/read/29802207/regulatory-t-cells-induce-activation-rather-than-suppression-of-human-basophils
#18
Meenu Sharma, Mrinmoy Das, Emmanuel Stephen-Victor, Caroline Galeotti, Anupama Karnam, Mohan S Maddur, Patrick Bruneval, Srini V Kaveri, Jagadeesh Bayry
Basophils are a rare granulocyte population that has been associated with allergic and inflammatory responses. It is essential to understand the regulatory mechanisms by which basophils are kept in check, considering the impact of dysregulated basophil function on immune responses under different pathological conditions. Among immunoregulatory cells, CD4+ CD25+ FoxP3+ regulatory T cells (Tregs ) are the key players that maintain immune tolerance. The mechanisms by which Tregs regulate and suppress diverse immune cell subsets have been studied extensively, but the impact of Tregs on basophil functions is not well understood...
May 25, 2018: Science Immunology
https://www.readbyqxmd.com/read/29776993/tumor-immune-evasion-arises-through-loss-of-tnf-sensitivity
#19
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
https://www.readbyqxmd.com/read/29752301/mitochondrial-cyclophilin-d-regulates-t-cell-metabolic-responses-and-disease-tolerance-to-tuberculosis
#20
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
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