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Science Immunology

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https://www.readbyqxmd.com/read/30446505/single-cell-transcriptional-analysis-reveals-ilc-like-cells-in-zebrafish
#1
Pedro P Hernández, Paulina M Strzelecka, Emmanouil I Athanasiadis, Dominic Hall, Ana F Robalo, Catherine M Collins, Pierre Boudinot, Jean-Pierre Levraud, Ana Cvejic
Innate lymphoid cells (ILCs) are important mediators of the immune response and homeostasis in barrier tissues of mammals. However, the existence and function of ILCs in other vertebrates are poorly understood. Here, we use single-cell RNA sequencing to generate a comprehensive atlas of zebrafish lymphocytes during tissue homeostasis and after immune challenge. We profiled 14,080 individual cells from the gut of wild-type zebrafish, as well as of rag1 -deficient zebrafish that lack T and B cells, and discovered populations of ILC-like cells...
November 16, 2018: Science Immunology
https://www.readbyqxmd.com/read/30413420/inhibitory-killer-cell-immunoglobulin-like-receptors-strengthen-cd8-t-cell-mediated-control-of-hiv-1-hcv-and-htlv-1
#2
Lies Boelen, Bisrat Debebe, Marcos Silveira, Arafa Salam, Julia Makinde, Chrissy H Roberts, Eddie C Y Wang, John Frater, Jill Gilmour, Katie Twigger, Kristin Ladell, Kelly L Miners, Jyothi Jayaraman, James A Traherne, David A Price, Ying Qi, Maureen P Martin, Derek C Macallan, Chloe L Thio, Jacquie Astemborski, Gregory Kirk, Sharyne M Donfield, Susan Buchbinder, Salim I Khakoo, James J Goedert, John Trowsdale, Mary Carrington, Simon Kollnberger, Becca Asquith
Killer cell immunoglobulin-like receptors (KIRs) are expressed predominantly on natural killer cells, where they play a key role in the regulation of innate immune responses. Recent studies show that inhibitory KIRs can also affect adaptive T cell-mediated immunity. In mice and in human T cells in vitro, inhibitory KIR ligation enhanced CD8+ T cell survival. To investigate the clinical relevance of these observations, we conducted an extensive immunogenetic analysis of multiple independent cohorts of HIV-1-, hepatitis C virus (HCV)-, and human T cell leukemia virus type 1 (HTLV-1)-infected individuals in conjunction with in vitro assays of T cell survival, analysis of ex vivo KIR expression, and mathematical modeling of host-virus dynamics...
November 9, 2018: Science Immunology
https://www.readbyqxmd.com/read/30389801/a-sweet-alternative-maintaining-m2-macrophage-polarization
#3
Anouk A J Hamers, Asha B Pillai
Glycolytic metabolism functions as a backup mechanism for M2 macrophage polarization when oxidative phosphorylation is disrupted.
November 2, 2018: Science Immunology
https://www.readbyqxmd.com/read/30389800/trypping-up-antigenic-variation-in-sleeping-sickness
#4
Gabriel K Griffin
Histone variants ensure proper genome partitioning in trypanosomes to restrict antigenic variation.
November 2, 2018: Science Immunology
https://www.readbyqxmd.com/read/30389799/developing-combination-immunotherapies-against-cancer-that-make-sense
#5
REVIEW
André Veillette, Dominique Davidson
Mechanistic preclinical studies provide a compelling case that combination immunotherapies that target the receptors PD-1 and GITR may demonstrate synergy in human cancer.
November 2, 2018: Science Immunology
https://www.readbyqxmd.com/read/30389798/clonal-expansion-and-compartmentalized-maintenance-of-rhesus-macaque-nk-cell-subsets
#6
Chuanfeng Wu, Diego A Espinoza, Samson J Koelle, Di Yang, Lauren Truitt, Heinrich Schlums, Bernard A Lafont, Jan K Davidson-Moncada, Rong Lu, Amitinder Kaur, Quirin Hammer, Brian Li, Sandhya Panch, David A Allan, Robert E Donahue, Richard W Childs, Chiara Romagnani, Yenan T Bryceson, Cynthia E Dunbar
Natural killer (NK) cells recognize and eliminate infected and malignant cells. Their life histories are poorly understood, particularly in humans, due to lack of informative models and endogenous clonal markers. Here, we apply transplantation of barcoded rhesus macaque hematopoietic cells to interrogate the landscape of NK cell production, expansion, and life histories at a clonal level long term and after proliferative challenge. We identify oligoclonal populations of rhesus CD56- CD16+ NK cells that are characterized by marked expansions and contractions over time yet remained long-term clonally uncoupled from other hematopoietic lineages, including CD56+ CD16- NK cells...
November 2, 2018: Science Immunology
https://www.readbyqxmd.com/read/30389797/-combination-cancer-immunotherapy-targeting-pd-1-and-gitr-can-rescue-cd8-t-cell-dysfunction-and-maintain-memory-phenotype
#7
Bei Wang, Wen Zhang, Vladimir Jankovic, Jacquelynn Golubov, Patrick Poon, Erin M Oswald, Cagan Gurer, Joyce Wei, Ilyssa Ramos, Qi Wu, Janelle Waite, Min Ni, Christina Adler, Yi Wei, Lynn Macdonald, Tracey Rowlands, Susannah Brydges, Jean Siao, William Poueymirou, Douglas MacDonald, George D Yancopoulos, Matthew A Sleeman, Andrew J Murphy, Dimitris Skokos
Most patients with cancer do not develop durable antitumor responses after programmed cell death protein 1 (PD-1) or programmed cell death ligand 1(PD-L1) checkpoint inhibition monotherapy because of an ephemeral reversal of T cell dysfunction and failure to promote long-lasting immunological T cell memory. Activating costimulatory pathways to induce stronger T cell activation may improve the efficacy of checkpoint inhibition and lead to durable antitumor responses. We performed single-cell RNA sequencing of more than 2000 tumor-infiltrating CD8+ T cells in mice receiving both PD-1 and GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) antibodies and found that this combination synergistically enhanced the effector function of expanded CD8+ T cells by restoring the balance of key homeostatic regulators CD226 and T cell immunoreceptor with Ig and ITIM domains (TIGIT), leading to a robust survival benefit...
November 2, 2018: Science Immunology
https://www.readbyqxmd.com/read/30366940/type-3-cytokines-il-17a-and-il-22-drive-tgf-%C3%AE-dependent-liver-fibrosis
#8
Thomas Fabre, Manuel Flores Molina, Geneviève Soucy, Jean-Philippe Goulet, Bernard Willems, Jean-Pierre Villeneuve, Marc Bilodeau, Naglaa H Shoukry
Inflammatory immune cells can modulate activation of hepatic stellate cells (HSCs) and progression of liver fibrosis. Type 3 inflammation characterized by production of interleukin-17A (IL-17) and IL-22 by innate and adaptive immune cells is implicated in many inflammatory conditions of the gut and can be counteracted by regulatory T cells (Tregs ), but its contribution to liver fibrosis is still poorly understood. Here, we evaluated the contribution of type 3 inflammation in liver fibrosis using clinical liver biopsies, in vitro stimulation of primary HSCs, and in vivo mouse models...
October 26, 2018: Science Immunology
https://www.readbyqxmd.com/read/30341146/glycans-for-good
#9
REVIEW
Katherine A Kaiser, Nicholas Arpaia
The gut commensal bacterium Bifidobacterium bifidum promotes immune tolerance by facilitating the induction of colonic regulatory T cells.
October 19, 2018: Science Immunology
https://www.readbyqxmd.com/read/30341145/cell-surface-polysaccharides-of-bifidobacterium-bifidum-induce-the-generation-of-foxp3-regulatory-t-cells
#10
Ravi Verma, Changhon Lee, Eun-Ji Jeun, Jaeu Yi, Kwang Soon Kim, Ambarnil Ghosh, Seohyun Byun, Choong-Gu Lee, Hye-Ji Kang, Gi-Cheon Kim, Chang-Duk Jun, Gwenaël Jan, Chang-Hee Suh, Ju-Yang Jung, Jonathan Sprent, Dipayan Rudra, Cristina De Castro, Antonio Molinaro, Charles D Surh, Sin-Hyeog Im
Dysregulation of intestinal microflora is linked to inflammatory disorders associated with compromised immunosuppressive functions of Foxp3+ T regulatory (Treg ) cells. Although mucosa-associated commensal microbiota has been implicated in Treg generation, molecular identities of the "effector" components controlling this process remain largely unknown. Here, we have defined Bifidobacterium bifidum as a potent inducer of Foxp3+ Treg cells with diverse T cell receptor specificity to dietary antigens, commensal bacteria, and B...
October 19, 2018: Science Immunology
https://www.readbyqxmd.com/read/30315122/a-subset-of-hla-i-peptides-are-not-genomically-templated-evidence-for-cis-and-trans-spliced-peptide-ligands
#11
Pouya Faridi, Chen Li, Sri H Ramarathinam, Julian P Vivian, Patricia T Illing, Nicole A Mifsud, Rochelle Ayala, Jiangning Song, Linden J Gearing, Paul J Hertzog, Nicola Ternette, Jamie Rossjohn, Nathan P Croft, Anthony W Purcell
The diversity of peptides displayed by class I human leukocyte antigen (HLA) plays an essential role in T cell immunity. The peptide repertoire is extended by various posttranslational modifications, including proteasomal splicing of peptide fragments from distinct regions of an antigen to form nongenomically templated cis-spliced sequences. Previously, it has been suggested that a fraction of the immunopeptidome constitutes such cis-spliced peptides; however, because of computational limitations, it has not been possible to assess whether trans-spliced peptides (i...
October 12, 2018: Science Immunology
https://www.readbyqxmd.com/read/30291134/b-cells-drive-auto-t-cells-to-the-brain
#12
Jenna L Pappalardo, Kevin C O'Connor
Self-reactive T cells that traffic to the brain tissue of patients with multiple sclerosis are driven by antigen-experienced B cells.
October 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/30291133/checking-into-the-germinal-centers-pd-1-regulates-entry
#13
Stephanie C Eisenbarth
PD-1 functions on T follicular helper cells to dictate localization within lymph node germinal centers.
October 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/30291132/airway-brush-cells-not-as-tuft-as-you-might-think
#14
REVIEW
Tiffany Bouchery, Benjamin J Marsland
The leukotriene E4 receptor CysLT3 R regulates expansion of chemosensory brush cells and production of interleukin-25 in the airways.
October 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/30291131/the-cysteinyl-leukotriene-3-receptor-regulates-expansion-of-il-25-producing-airway-brush-cells-leading-to-type-2-inflammation
#15
Lora G Bankova, Daniel F Dwyer, Eri Yoshimoto, Saltanat Ualiyeva, John W McGinty, Hannah Raff, Jakob von Moltke, Yoshihide Kanaoka, K Frank Austen, Nora A Barrett
Respiratory epithelial cells (EpCs) orchestrate airway mucosal inflammation in response to diverse environmental stimuli, but how distinct EpC programs are regulated remains poorly understood. Here, we report that inhalation of aeroallergens leads to expansion of airway brush cells (BrCs), specialized chemosensory EpCs and the dominant epithelial source of interleukin-25 (IL-25). BrC expansion was attenuated in mice lacking either LTC4 synthase, the biosynthetic enzyme required for cysteinyl leukotriene (CysLT) generation, or the EpC receptor for leukotriene E4 (LTE4 ), CysLT3 R...
October 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/30291130/emergence-of-immunoregulatory-ym1-ly6c-hi-monocytes-during-recovery-phase-of-tissue-injury
#16
Naoki Ikeda, Kenichi Asano, Kenta Kikuchi, Yoshimi Uchida, Hiroki Ikegami, Ryo Takagi, Satoshi Yotsumoto, Takumi Shibuya, Chieko Makino-Okamura, Hidehiro Fukuyama, Takashi Watanabe, Masaki Ohmuraya, Kimi Araki, Gen Nishitai, Masato Tanaka
Ly6Chi monocytes migrate to injured sites and induce inflammation in the acute phase of tissue injury. However, once the causes of tissue injury are eliminated, monocyte-derived macrophages contribute to the resolution of inflammation and tissue repair. It remains unclear whether the emergence of these immunoregulatory macrophages is attributed to the phenotypic conversion of inflammatory monocytes in situ or to the recruitment of bone marrow-derived regulatory cells de novo. Here, we identified a subpopulation of Ly6Chi monocytes that contribute to the resolution of inflammation and tissue repair...
October 5, 2018: Science Immunology
https://www.readbyqxmd.com/read/30266866/the-probacterial-effect-of-type-i-interferon-signaling-requires-its-own-negative-regulator-usp18
#17
Namir Shaabani, Nadine Honke, Nhan Nguyen, Zhe Huang, Kei-Ichiro Arimoto, Daniel Lazar, Taylor K Loe, Karl S Lang, Marco Prinz, Klaus-Peter Knobeloch, Dong-Er Zhang, John R Teijaro
Type I interferon (IFN-I) signaling paradoxically impairs host immune responses during many primary and secondary bacterial infections. Lack of IFN-I receptor reduces bacterial replication and/or bacterial persistence during infection with several bacteria. However, the mechanisms that mediate the adverse IFN-I effect are incompletely understood. Here, we show that Usp18 , an interferon-stimulated gene that negatively regulates IFN-I signaling, is primarily responsible for the deleterious effect of IFN-I signaling during infection of mice with Listeria monocytogenes or Staphylococcus aureus Mechanistically, USP18 promoted bacterial replication by inhibiting antibacterial tumor necrosis factor-α (TNF-α) signaling...
September 28, 2018: Science Immunology
https://www.readbyqxmd.com/read/30242080/enhancing-fc%C3%AE-r-mediated-antibody-effector-function-during-persistent-viral-infection
#18
Andreas Wieland, Alice O Kamphorst, Rajesh M Valanparambil, Jin-Hwan Han, Xiaojin Xu, Biswa P Choudhury, Rafi Ahmed
Persistent viral infections can interfere with FcγR-mediated antibody effector functions by excessive immune complex (IC) formation, resulting in resistance to therapeutic FcγR-dependent antibodies. We and others have previously demonstrated that mice persistently infected with lymphocytic choriomeningitis virus (LCMV) are resistant to a wide range of depleting antibodies due to excessive IC formation. Here, we dissect the mechanisms by which two depleting antibodies overcome the obstacle of endogenous ICs and achieve efficient target cell depletion in persistently infected mice...
September 21, 2018: Science Immunology
https://www.readbyqxmd.com/read/30217812/a-fresh-approach-combining-basic-science-and-social-good
#19
EDITORIAL
Thumbi Ndung'u, Krista L Dong, Douglas S Kwon, Bruce D Walker
A program to study HIV infection is empowering African women.
September 14, 2018: Science Immunology
https://www.readbyqxmd.com/read/30217811/molecular-diversification-of-regulatory-t-cells-in-nonlymphoid-tissues
#20
Joanna R DiSpirito, David Zemmour, Deepshika Ramanan, Jun Cho, Rapolas Zilionis, Allon M Klein, Christophe Benoist, Diane Mathis
Foxp3+ CD4+ regulatory T cells (Tregs ) accumulate in certain nonlymphoid tissues, where they control diverse aspects of organ homeostasis. Populations of tissue Tregs , as they have been termed, have transcriptomes distinct from those of their counterparts in lymphoid organs and other nonlymphoid tissues. We examined the diversification of Tregs in visceral adipose tissue, skeletal muscle, and the colon vis-à-vis lymphoid organs from the same individuals. The unique transcriptomes of the various tissue Treg populations resulted from layering of tissue-restricted open chromatin regions over regions already open in the spleen, the latter tagged by super-enhancers and particular histone marks...
September 14, 2018: Science Immunology
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