Multifunctional Pan-ebolavirus Antibody Recognizes a Site of Broad Vulnerability on the Ebolavirus Glycoprotein
Gilchuk et  al. isolated and characterized new broadly neutralizing human monoclonal antibodies active against all three clinically relevant ebolaviruses. Some potent antibodies bind to the glycoprotein base region, act principally by direct virus neutralization, and exploit several mechanisms for contributin g to pan-ebolavirus protective immunity. (Source: Immunity)
Source: Immunity - July 17, 2018 Category: Allergy & Immunology Authors: Pavlo Gilchuk, Natalia Kuzmina, Philipp A. Ilinykh, Kai Huang, Bronwyn M. Gunn, Aubrey Bryan, Edgar Davidson, Benjamin J. Doranz, Hannah L. Turner, Marnie L. Fusco, Matthew S. Bramble, Nicole A. Hoff, Elad Binshtein, Nurgun Kose, Andrew I. Flyak, Robin Fl Tags: Article Source Type: research

LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells
Plasma cells secrete antibodies and play a key role in host defense against infection. Lino et  al. identify a novel subset of natural regulatory plasma cells characterized by the expression of LAG-3 that develops at steady state independently of microbiota, and respond to innate stimulation by producing immunosuppressive IL-10. (Source: Immunity)
Source: Immunity - July 10, 2018 Category: Allergy & Immunology Authors: Andreia C. Lino, Van Duc Dang, Vicky Lampropoulou, Anna Welle, Jara Joedicke, Jelka Pohar, Quentin Simon, Jessie Thalmensi, Aurelia Baures, Vinciane Fl ühler, Imme Sakwa, Ulrik Stervbo, Stefanie Ries, Luc Jouneau, Pierre Boudinot, Takeshi Tsubata, Takahi Tags: Article Source Type: research

Critical Role for the Microbiota in CX3CR1+ Intestinal Mononuclear Phagocyte Regulation of Intestinal T  Cell Responses
Host microbiota interactions regulate many aspects of immunity. Kim et  al. demonstrate that microbial adhesion to intestinal epithelium helps regulate the balance between pro- and anti-inflammatory T cell responses through induction of IL-10 by a subset of intestinal antigen-presenting cells. (Source: Immunity)
Source: Immunity - July 3, 2018 Category: Allergy & Immunology Authors: Myunghoo Kim, Carolina Galan, Andrea A. Hill, Wan-Jung Wu, Hannah Fehlner-Peach, Hyo Won Song, Deborah Schady, Matthew L. Bettini, Kenneth W. Simpson, Randy S. Longman, Dan R. Littman, Gretchen E. Diehl Tags: Article Source Type: research

Gain-of-Function Mutation of Card14 Leads to Spontaneous Psoriasis-like Skin Inflammation through Enhanced Keratinocyte Response to IL-17A
Mutations in the CARMA2 gene (CARD14) are identified in psoriasis patients, but whether and how these mutations initiate psoriasis is unclear. Wang et  al. reveal that Card14E138A/+ mice develop spontaneous psoriasis via CARMA2 self-aggregation and activation, and the deficiency or mutation of Card14 affects the activation of IL-17A signaling in keratinocytes. (Source: Immunity)
Source: Immunity - July 3, 2018 Category: Allergy & Immunology Authors: Mingchao Wang, Shanshan Zhang, Guoxing Zheng, Junjiu Huang, Zhou Songyang, Xueqiang Zhao, Xin Lin Tags: Article Source Type: research

TRPV4 Channel Signaling in Macrophages Promotes Gastrointestinal Motility via Direct Effects on Smooth Muscle Cells
How intestinal macrophages regulate intestinal motility remains poorly understood. Luo et  al. demonstrate that muscularis macrophages expressing the TRPV4 channel promote GI motility by directly affecting the function of intestinal smooth muscle cells independent of the enteric nervous system. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Jialie Luo, Aihua Qian, Landon K. Oetjen, Weihua Yu, Pu Yang, Jing Feng, Zili Xie, Shenbin Liu, Shijin Yin, Dari Dryn, Jizhong Cheng, Terrence E. Riehl, Alexander V. Zholos, William F. Stenson, Brian S. Kim, Hongzhen Hu Tags: Article Source Type: research

Amphiregulin-Producing Pathogenic Memory T Helper 2 Cells Instruct Eosinophils to Secrete Osteopontin and Facilitate Airway Fibrosis
Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. Morimoto and colleagues find that the IL-33-ST2-amphiregulin-EGRF-osteopontin axis directs fibrotic responses in chronic allergic inflammation with the involvement of airway epithelial cells, pathogenic memory Th2 cells, and inflammatory eosinophils in both mouse and human. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Yuki Morimoto, Kiyoshi Hirahara, Masahiro Kiuchi, Tomoko Wada, Tomomi Ichikawa, Toshio Kanno, Mikiko Okano, Kota Kokubo, Atsushi Onodera, Daiju Sakurai, Yoshitaka Okamoto, Toshinori Nakayama Tags: Article Source Type: research

The TWIK2 Potassium Efflux Channel in Macrophages Mediates NLRP3 Inflammasome-Induced Inflammation
Potassium efflux is required for NLRP3 inflammasome activation, but the channel mediating the efflux has remained elusive. Di et  al. identify the potassium channel TWIK2 as a mediator of potassium efflux and NLRP3 activation in macrophages. Targeting TWIK2 could form the basis for therapeutic approaches in inflammatory injury. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Anke Di, Shiqin Xiong, Zhiming Ye, R.K. Subbarao Malireddi, Satoshi Kometani, Ming Zhong, Manish Mittal, Zhigang Hong, Thirumala-Devi Kanneganti, Jalees Rehman, Asrar B. Malik Tags: Article Source Type: research

Sympathetic Neuronal Activation Triggers Myeloid Progenitor Proliferation and Differentiation
Neural control of immunity and inflammation has been reported. Vasamsetti and colleagues demonstrate that the sympathetic nervous system controls the development of inflammatory myeloid cells from their progenitors in inflammatory conditions. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Sathish Babu Vasamsetti, Jonathan Florentin, Emilie Coppin, Lotte C.A. Stiekema, Kang H. Zheng, Muhammad Umer Nisar, John Sembrat, David J. Levinthal, Mauricio Rojas, Erik S.G. Stroes, Kang Kim, Partha Dutta Tags: Article Source Type: research

Virus-Induced Interferon- γ Causes Insulin Resistance in Skeletal Muscle and Derails Glycemic Control in Obesity
It is unknown how viral infections contribute to the progression of type 2 diabetes. Šestan and colleagues demonstrate that virus-induced interferon-γ increases muscle insulin resistance, which drives hyperinsulinemia to keep euglycemia and to boost anti-viral CD8+ T cell responses. This mechanism in obese subjects with hepatic IR derails glycemic control. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Marko Šestan, Sonja Marinović, Inga Kavazović, Đurđica Cekinović, Stephan Wueest, Tamara Turk Wensveen, Ilija Brizić, Stipan Jonjić, Daniel Konrad, Felix M. Wensveen, Bojan Polić Tags: Article Source Type: research

Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1-Mediated Proinflammatory Cytokine Production
Iron accumulation is observed in the brain of patients with neuroinflammatory diseases, yet its functional significance is poorly understood. Wang et  al. demonstrate that iron promotes T cell pathogenicity by protecting RNA-binding protein PCBP1 from proteolysis, thereby promoting PCBP1-mediated stabilization of GM-CSF mRNA. These findings indicate that iron homeostasis can be targeted to suppress pathogenic T cells for treatment of neuroinfl ammatory diseases. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Zhizhang Wang, Weijie Yin, Lizhen Zhu, Jia Li, Yikun Yao, Feifei Chen, Mengmeng Sun, Jiayuan Zhang, Nan Shen, Yan Song, Xing Chang Tags: Article Source Type: research

Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy
Using a library of pancreatic cancer cell clones, Li et  al. identify heterogeneous and multifactorial pathways regulating tumor-cell-intrinsic mechanisms that dictate the immune microenvironment and thereby responses to immunotherapy. This tumor clone library provides a tool for identifying new targets responsible for thwarting responses to immunothera py in resistant tumors. (Source: Immunity)
Source: Immunity - June 26, 2018 Category: Allergy & Immunology Authors: Jinyang Li, Katelyn T. Byrne, Fangxue Yan, Taiji Yamazoe, Zeyu Chen, Timour Baslan, Lee P. Richman, Jeffrey H. Lin, Yu H. Sun, Andrew J. Rech, David Balli, Ceire A. Hay, Yogev Sela, Allyson J. Merrell, Shannon M. Liudahl, Naomi Gordon, Robert J. Norgard, Tags: Article Source Type: research

Tissue-Restricted Adaptive Type 2 Immunity Is Orchestrated by Expression of the Costimulatory Molecule OX40L on Group 2 Innate Lymphoid Cells
Type 2 immunity underpins diverse processes central to tissue homeostasis, allergic inflammation, and anti-helminth immunity. Halim et  al. demonstrate that the local expansion of Th2 and Treg cells in response to the alarmin IL-33 is dependent on the expression of the costimulatory molecule OX40L by type 2 innate lymphoid cells (ILC2s), revealing a central role for the IL-33-ILC2-OX40L pathway in the orchestration of type 2 immun ity. (Source: Immunity)
Source: Immunity - June 12, 2018 Category: Allergy & Immunology Authors: Timotheus Y.F. Halim, Batika M.J. Rana, Jennifer A. Walker, Bernhard Kerscher, Martin D. Knolle, Helen E. Jolin, Eva M. Serrao, Liora Haim-Vilmovsky, Sarah A. Teichmann, Hans-Reimer Rodewald, Marina Botto, Timothy J. Vyse, Padraic G. Fallon, Zhi Li, David Tags: Article Source Type: research

A Single-Cell Transcriptomic Atlas of Thymus Organogenesis Resolves Cell Types and Developmental Maturation
Studies of thymus development typically lack single-cell resolution, use indirect readouts, or target narrow cell subsets. Using single-cell RNA sequencing during thymus organogenesis, Kernfeld and Genga et  al. reveal cellular heterogeneity, interrogate developmental dynamics by direct observation, and pinpoint cell-specific expression patterns in stromal and blood populations. (Source: Immunity)
Source: Immunity - June 5, 2018 Category: Allergy & Immunology Authors: Eric M. Kernfeld, Ryan M.J. Genga, Kashfia Neherin, Margaret E. Magaletta, Ping Xu, Ren é Maehr Tags: Resource Source Type: research

Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM+ and Transient IgG+ Memory B Cells
Immunity induced by certain vaccines declines over time. By studying B cell responses to phycoerythrin, Pape et  al. find that memory B cells can be short-lived when generated from precursors that experience unusually strong early signals through their un-mutated antigen receptors. (Source: Immunity)
Source: Immunity - June 5, 2018 Category: Allergy & Immunology Authors: Kathryn A. Pape, Robert W. Maul, Thamotharampillai Dileepan, Amanda Schmidt Paustian, Patricia J. Gearhart, Marc K. Jenkins Tags: Article Source Type: research

Protein Kinase C- β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis
Lymphocyte activation is associated with major changes in metabolism. Tsui and colleagues demonstrate that PKC β promotes metabolic reprogramming to drive effector fate decision in B cells. (Source: Immunity)
Source: Immunity - June 5, 2018 Category: Allergy & Immunology Authors: Carlson Tsui, Nuria Martinez-Martin, Mauro Gaya, Paula Maldonado, Miriam Llorian, Nathalie M. Legrave, Merja Rossi, James I. MacRae, Angus J. Cameron, Peter J. Parker, Michael Leitges, Andreas Bruckbauer, Facundo D. Batista Tags: Article Source Type: research

The Tumor Necrosis Factor Superfamily Member RANKL Suppresses Effector Cytokine Production in Group 3 Innate Lymphoid Cells
Although signals that activate group 3  ILCs (ILC3s) have been described, the factors that negatively regulate these cells are less well understood. Bando et al. demonstrate that the TNF superfamily member RANKL suppresses the abundance and effector functions of intestinal CCR6+ ILC3s and that RANKL-mediated suppression occurs through ILC3-ILC3 interactions. (Source: Immunity)
Source: Immunity - May 29, 2018 Category: Allergy & Immunology Authors: Jennifer K. Bando, Susan Gilfillan, Christina Song, Keely G. McDonald, Stanley C.-C. Huang, Rodney D. Newberry, Yasuhiro Kobayashi, David S.J. Allan, James R. Carlyle, Marina Cella, Marco Colonna Tags: Article Source Type: research

Extrathymically Generated Regulatory T Cells Establish a Niche for Intestinal Border-Dwelling Bacteria and Affect Physiologic Metabolite Balance
Extrathymically generated regulatory (pTreg) cells are induced by bacterial products at mucosal sites. In this issue, Campbell et  al. show that pTreg cell deficiency impedes the establishment of a subset of intestinal bacteria due to heightened immune responses, with significant effects on host metabolites and fitness. (Source: Immunity)
Source: Immunity - May 29, 2018 Category: Allergy & Immunology Authors: Clarissa Campbell, Stanislav Dikiy, Shakti K. Bhattarai, Takatoshi Chinen, Fanny Matheis, Marco Calafiore, Beatrice Hoyos, Alan Hanash, Daniel Mucida, Vanni Bucci, Alexander Y. Rudensky Tags: Article Source Type: research

Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion
How Shigella can be infectious in humans despite lacking clear mechanisms for mucosal adhesion remains a long-standing enigma concerning its pathogenesis. Xu et  al. demonstrate that Shigella exploits the host defense peptide HD5 in the gut to attain its ability to colonize and destroy the intestinal epithelium. (Source: Immunity)
Source: Immunity - May 29, 2018 Category: Allergy & Immunology Authors: Dan Xu, Chongbing Liao, Bing Zhang, W. David Tolbert, Wangxiao He, Zhijun Dai, Wei Zhang, Weirong Yuan, Marzena Pazgier, Jiankang Liu, Jun Yu, Philippe J. Sansonetti, Charles L. Bevins, Yongping Shao, Wuyuan Lu Tags: Article Source Type: research

Transcription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response
The link between human IRF8 mutations and immunodeficiency is poorly understood. Adams et  al. demonstrate that IRF8 is required for NK-cell-mediated antiviral immunity by promoting proliferation of virus-specific NK cells. (Source: Immunity)
Source: Immunity - May 29, 2018 Category: Allergy & Immunology Authors: Nicholas M. Adams, Colleen M. Lau, Xiying Fan, Moritz Rapp, Clair D. Geary, Orr-El Weizman, Carlos Diaz-Salazar, Joseph C. Sun Tags: Article Source Type: research

Hemogenic Endothelial Fate Mapping Reveals Dual Developmental Origin of Mast Cells
Gentek et  al. demonstrate that Cdh5-CreERT2 can be used to selectively fate map yolk sac and definitive hematopoiesis. Temporally defined Cdh5-CreERT2 lineage tracing reveals that mast cells are yolk sac derived in the embryo but replaced by definitive hematopoiesis in the adult, a feature they share with m acrophages. (Source: Immunity)
Source: Immunity - May 29, 2018 Category: Allergy & Immunology Authors: Rebecca Gentek, Cl ément Ghigo, Guillaume Hoeffel, Maxime Jacques Bulle, Rasha Msallam, Gregory Gautier, Pierre Launay, Jinmiao Chen, Florent Ginhoux, Marc Bajénoff Tags: Article Source Type: research

Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4+ T Cells
The host factors that promote the survival and persistence of HIV-infected CD4+ T  cells are not clear. Kuo et al. demonstrate that the anti-apoptotic protein BIRC5 and its upstream regulator OX40 can promote survival of HIV-1-infected reservoir CD4+ T cells, specifically during clonal proliferation. These findings point to clinical strategies that may reduce persisting viral reservoirs. (Source: Immunity)
Source: Immunity - May 22, 2018 Category: Allergy & Immunology Authors: Hsiao-Hsuan Kuo, Rushdy Ahmad, Guinevere Q. Lee, Ce Gao, Hsiao-Rong Chen, Zhengyu Ouyang, Matthew J. Szucs, Dhohyung Kim, Athe Tsibris, Tae-Wook Chun, Emilie Battivelli, Eric Verdin, Eric S. Rosenberg, Steven A. Carr, Xu G. Yu, Mathias Lichterfeld Tags: Article Source Type: research

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis
In this study, Hirota et  al. identified in an animal model of rheumatoid arthritis an inflammatory cellular cascade instigated by an arthritogenic T helper subset and enhanced by GM-CSF-producing synovial-resident innate lymphoid cells. (Source: Immunity)
Source: Immunity - May 22, 2018 Category: Allergy & Immunology Authors: Keiji Hirota, Motomu Hashimoto, Yoshinaga Ito, Mayumi Matsuura, Hiromu Ito, Masao Tanaka, Hitomi Watanabe, Gen Kondoh, Atsushi Tanaka, Keiko Yasuda, Manfred Kopf, Alexandre J. Potocnik, Brigitta Stockinger, Noriko Sakaguchi, Shimon Sakaguchi Tags: Article Source Type: research

Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity
Lymph node stromal cells support diverse processes, but bulk assessments obscure their niche-specific functions. Rodda et  al. identify transcriptional profiles for nine lymph node stromal cell clusters using single-cell RNA sequencing, validate subset markers in situ, and suggest niche-restricted functions. (Source: Immunity)
Source: Immunity - May 8, 2018 Category: Allergy & Immunology Authors: Lauren B. Rodda, Erick Lu, Mariko L. Bennett, Caroline L. Sokol, Xiaoming Wang, Sanjiv A. Luther, Ben A. Barres, Andrew D. Luster, Chun Jimmie Ye, Jason G. Cyster Tags: Resource Source Type: research

CD36 Mediates Cell-Surface Antigens to Promote Thymic Development of the Regulatory T Cell Receptor Repertoire and Allo-tolerance
How cooperative antigen presentation between medullary thymic epithelial cells (mTECs) and dendritic cells (DCs) occurs remains unknown. Perry et  al. show that CD36, a scavenger receptor expressed on CD8α+ DCs, mediates acquisition and presentation of cell-surface antigens from mTECs for T cell receptor repertoire development and allo-tolerance during bone marrow transplantation. (Source: Immunity)
Source: Immunity - May 8, 2018 Category: Allergy & Immunology Authors: Justin S.A. Perry, Emilie V. Russler-Germain, You W. Zhou, Whitney Purtha, Matthew L. Cooper, Jaebok Choi, Mark A. Schroeder, Vanessa Salazar, Takeshi Egawa, Byeong-Chel Lee, Nada A. Abumrad, Brian S. Kim, Mark S. Anderson, John F. DiPersio, Chyi-Song Hsi Tags: Article Source Type: research

Proteomic Analyses of Human Regulatory T Cells Reveal Adaptations in Signaling Pathways that Protect Cellular Identity
Using high-resolution mass spectrometry and transcriptomics, Cuadrado et  al. provide a molecular characterization of regulatory and conventional CD4+ T cell subsets, yielding markers to distinguish cells with different properties and insights into mechanisms that prevent regulatory T cells from exhibiting undesirable functional activities of the related but functiona lly antithetical conventional T cells. (Source: Immunity)
Source: Immunity - May 8, 2018 Category: Allergy & Immunology Authors: Eloy Cuadrado, Maartje van den Biggelaar, Sander de Kivit, Yi-yen Chen, Manon Slot, Ihsane Doubal, Alexander Meijer, Rene A.W. van Lier, Jannie Borst, Derk Amsen Tags: Resource Source Type: research

Cell-Specific Imd-NF- κB Responses Enable Simultaneous Antibacterial Immunity and Intestinal Epithelial Cell Shedding upon Bacterial Infection
The intestinal epithelium is constantly renewed through cell shedding and stem cell activation, and this renewal maintains intestinal barrier integrity. Zhai et  al. show that in Drosophila, activation of the Imd-NF-κB pathway upon bacterial infection not only induces the expression of antimicrobial peptides, but also controls epithelial shedding, suggesting an evolutionarily conserved crosstalk between immunity and epithelial turnover. (Source: Immunity)
Source: Immunity - May 8, 2018 Category: Allergy & Immunology Authors: Zongzhao Zhai, Jean-Philippe Boquete, Bruno Lemaitre Tags: Article Source Type: research

The Microglial Innate Immune Receptor TREM2 Is Required for Synapse Elimination and Normal Brain Connectivity
TREM2 is a microglial innate immune receptor whose functions during brain development are still unknown. Filipello et  al. demonstrate that TREM2 is essential for microglia to eliminate supernumerary synapses in the developing brain. TREM2 protein was also reduced in autistic patients, suggesting that the receptor may be involved in neurodevelopmental diseases. (Source: Immunity)
Source: Immunity - May 8, 2018 Category: Allergy & Immunology Authors: Fabia Filipello, Raffaella Morini, Irene Corradini, Valerio Zerbi, Alice Canzi, Bernadeta Michalski, Marco Erreni, Marija Markicevic, Chiara Starvaggi-Cucuzza, Karel Otero, Laura Piccio, Francesca Cignarella, Fabio Perrucci, Matteo Tamborini, Marco Genua, Tags: Article Source Type: research

Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses
The cGAS-STING pathway is required for host defense against DNA viruses. Wang et  al. find that upon virus infection, Manganese (Mn2+) is released from organelles into the cytosol and facilitates the activation of cGAS and STING. Their findings identify a role for Mn in innate immune activation and host anti-viral defense. (Source: Immunity)
Source: Immunity - April 10, 2018 Category: Allergy & Immunology Authors: Chenguang Wang, Yukun Guan, Mengze Lv, Rui Zhang, Zhaoying Guo, Xiaoming Wei, Xiaoxia Du, Jing Yang, Tong Li, Yi Wan, Xiaodong Su, Xiaojun Huang, Zhengfan Jiang Tags: Article Source Type: research

An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation
The inflammatory mechanism of psoriasis remains incompletely understood. In this issue, Xu et  al. identified IL-25 as a key pathogenic factor regulating the proliferation of keratinocytes and psoriasis development in an autocrine expression manner. (Source: Immunity)
Source: Immunity - April 10, 2018 Category: Allergy & Immunology Authors: Miao Xu, Huiping Lu, Young-Hee Lee, Yelin Wu, Kewei Liu, Yuling Shi, Haoran An, Jingren Zhang, Xiaohu Wang, Yuping Lai, Chen Dong Tags: Article Source Type: research

The Immune Landscape of Cancer
Thorsson et  al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implicat ions for identifying ways to advance research on immunotherapy. (Source: Immunity)
Source: Immunity - April 5, 2018 Category: Allergy & Immunology Authors: V ésteinn Thorsson, David L. Gibbs, Scott D. Brown, Denise Wolf, Dante S. Bortone, Tai-Hsien Ou Yang, Eduard Porta-Pardo, Galen F. Gao, Christopher L. Plaisier, James A. Eddy, Elad Ziv, Aedin C. Culhane, Evan O. Paull, I.K. Ashok Sivakumar, Andrew J. Gen Tags: Resource Source Type: research

Toll-like Receptor 9 Contains Two DNA Binding Sites that Function Cooperatively to Promote Receptor Dimerization and Activation
TLR9 recognizes DNAs with unmethylated CpG motifs and activates innate immune responses. Ohto et  al. identify another TLR9 binding motif, the 5′-xCx DNA motif, and determine the tertiary structure of TLR9 in complex with CpG and 5′-xCx DNAs to reveal a cooperative activation mechanism of TLR9 by two types of DNAs. (Source: Immunity)
Source: Immunity - April 3, 2018 Category: Allergy & Immunology Authors: Umeharu Ohto, Hanako Ishida, Takuma Shibata, Ryota Sato, Kensuke Miyake, Toshiyuki Shimizu Tags: Article Source Type: research

Interleukin-15 Complex Treatment Protects Mice from Cerebral Malaria by Inducing Interleukin-10-Producing Natural Killer Cells
NK cells can display both pro-inflammatory and regulatory function, but their role in the pathogenesis of malaria is not fully understood. Burrack et  al. demonstrate that IL-15 complex (IL-15C) therapy prevents mice from succumbing to experimental cerebral malaria (ECM). IL-15C treatment stimulates NK cells to produce IL-10, suppressing the pathogenic CD8+ T cell response during ECM. (Source: Immunity)
Source: Immunity - April 3, 2018 Category: Allergy & Immunology Authors: Kristina S. Burrack, Matthew A. Huggins, Emily Taras, Philip Dougherty, Christine M. Henzler, Rendong Yang, Sarah Alter, Emily K. Jeng, Hing C. Wong, Martin Felices, Frank Cichocki, Jeffrey S. Miller, Geoffrey T. Hart, Aaron J. Johnson, Stephen C. Jameson Tags: Article Source Type: research

KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity
Herndler-Brandstetter et  al. demonstrate that KLRG1+IL-7Rα+ effector CD8+ T cells downregulate KLRG1 in a Bach2-dependent manner and differentiate into long-lived circulating and tissue-resident “exKLRG1” memory cells. Developmental plasticity of KLRG1+ effector cells therefore drives functional diversity within mem ory T cell lineages and promotes enhanced anti-influenza and anti-tumor immunity. (Source: Immunity)
Source: Immunity - April 3, 2018 Category: Allergy & Immunology Authors: Dietmar Herndler-Brandstetter, Harumichi Ishigame, Ryo Shinnakasu, Valerie Plajer, Carmen Stecher, Jun Zhao, Melanie Lietzenmayer, Lina Kroehling, Akiko Takumi, Kohei Kometani, Takeshi Inoue, Yuval Kluger, Susan M. Kaech, Tomohiro Kurosaki, Takaharu Okada Tags: Article Source Type: research

A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion
Disrupting the balance between self-renewal and differentiation of HSCs leads to severe pathologic consequences. Xia et  al. identify a circular RNA cia-cGAS that is highly expressed in the nucleus of LT-HSCs. Under homeostatic conditions, cia-cGAS binds DNA sensor cGAS to block its synthase activity, protecting dormant LT-HSCs from cGAS-mediated exhaustion. (Source: Immunity)
Source: Immunity - April 3, 2018 Category: Allergy & Immunology Authors: Pengyan Xia, Shuo Wang, Buqing Ye, Ying Du, Chong Li, Zhen Xiong, Yuan Qu, Zusen Fan Tags: Article Source Type: research

Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8+ T Cells
Mechanisms driving T  cell exhaustion have not been understood. Li et al. demonstrate that B7S1 on tumor-infiltrating myeloid cells initiates exhaustion of activated CD8+ TILs through upregulating Eomes, thus proposing B7S1 as a promising target to enhance the efficacy of anti-PD-1 therapy. (Source: Immunity)
Source: Immunity - April 3, 2018 Category: Allergy & Immunology Authors: Jing Li, Younghee Lee, Yanjian Li, Yu Jiang, Huiping Lu, Wenjuan Zang, Xiaohong Zhao, Liguo Liu, Yang Chen, Haidong Tan, Zhiying Yang, Michael Q. Zhang, Tak W. Mak, Ling Ni, Chen Dong Tags: Article Source Type: research

A Neutralizing Antibody Recognizing Primarily N-linked Glycan Targets the Silent Face of the HIV Envelope
The center of the “silent face” on the HIV-1 envelope is shielded by glycans and has been devoid of antibody recognition. Zhou et al. identify the antibody VRC-PG05, which binds a glycan-dominated epitope at the silent face center and completes antibody recognition of all major exposed regions of the envelope tr imer. (Source: Immunity)
Source: Immunity - March 13, 2018 Category: Allergy & Immunology Authors: Tongqing Zhou, Anqi Zheng, Ulrich Baxa, Gwo-Yu Chuang, Ivelin S. Georgiev, Rui Kong, Sijy O ’Dell, Syed Shahzad-ul-Hussan, Chen-Hsiang Shen, Yaroslav Tsybovsky, Robert T. Bailer, Syna K. Gift, Mark K. Louder, Krisha McKee, Reda Rawi, Catherine H. Steven Tags: Article Source Type: research

Sensing Microbial Viability through Bacterial RNA Augments T Follicular Helper Cell and Antibody Responses
Live vaccines typically elicit augmented humoral responses, affording superior protection. Barbet et  al. report that innate detection of bacterial RNA, a signature of microbial viability, directs a heightened Tfh cell response. This response is extrinsic to B cells and dendritic cells and involves CX3CR1+CCR2– monocyte instruction of Tfh differentiation via TRIF-dependent IFN-β licensing of ba cterial RNA-driven inflammasome activation. (Source: Immunity)
Source: Immunity - March 13, 2018 Category: Allergy & Immunology Authors: Gaetan Barbet, Leif E. Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J. Magarian Blander Tags: Article Source Type: research

Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner
Little is known about the epigenetic signals that control microglia function in  vivo. Datta et al. show that histone deacetylases Hdac1 and Hdac2 are essential for microglial survival and expansion during development but not during steady state. In Alzheimer’s disease mouse model, deletion of microglial Hdac1 and Hdac2 reduces amyloid pathology and improves cognitive funct ion. (Source: Immunity)
Source: Immunity - March 13, 2018 Category: Allergy & Immunology Authors: Moumita Datta, Ori Staszewski, Elena Raschi, Maximilian Frosch, Nora Hagemeyer, Tuan Leng Tay, Thomas Blank, Mario Kreutzfeldt, Doron Merkler, Stephanie Ziegler-Waldkirch, Patrick Matthias, Melanie Meyer-Luehmann, Marco Prinz Tags: Article Source Type: research

Human IFIT3 Modulates IFIT1 RNA Binding Specificity and Protein Stability
Prior studies have suggested that human IFIT1, unlike its mouse ortholog, might not recognize viral RNA molecules lacking 2 ′-O methylation on their cap structures. Johnson et al. report a crystal structure between cap 0 (m7GpppN) RNA bound to human IFIT1 in complex with the C-terminal domain (CTD) of human IFIT3. The CTD of IFIT3 bound to IFIT1 and allosterically regulated the IFIT1 RNA-binding channel and promoted s elective recognition of cap 0 RNA. Functional studies demonstrated that IFIT3 interaction with IFIT1 was important for stabilizing IFIT1 expression and was required for restricting infection of vir...
Source: Immunity - March 7, 2018 Category: Allergy & Immunology Authors: Britney Johnson, Laura A. VanBlargan, Wei Xu, James P. White, Chao Shan, Pei-Yong Shi, Rong Zhang, Jagat Adhikari, Michael L. Gross, Daisy W. Leung, Michael S. Diamond, Gaya K. Amarasinghe Tags: Article Source Type: research

Mitochondria-Endoplasmic Reticulum Contact Sites Function as Immunometabolic Hubs that Orchestrate the Rapid Recall Response of Memory CD8+ T Cells
How glucose metabolism enables rapid acquisition of effector function in memory CD8+ T  cells remains poorly understood. Bantug et al. demonstrate that mitochondria-endoplasmic reticulum contact sites are signaling hubs that enable the metabolic reprogramming required for rapid CD8+ T cell recall responses. (Source: Immunity)
Source: Immunity - March 6, 2018 Category: Allergy & Immunology Authors: Glenn R. Bantug, Marco Fischer, Jasmin Gr ählert, Maria L. Balmer, Gunhild Unterstab, Leyla Develioglu, Rebekah Steiner, Lianjun Zhang, Ana S.H. Costa, Patrick M. Gubser, Anne-Valérie Burgener, Ursula Sauder, Jordan Löliger, Réka Belle, Sarah Dimeloe, Tags: Article Source Type: research

E3 Ligase VHL Promotes Group 2 Innate Lymphoid Cell Maturation and Function via Glycolysis Inhibition and Induction of Interleukin-33 Receptor
ILC2s are critically involved in allergic responses, but the mechanisms by which they are regulated remain unclear. Li et  al. demonstrate that the VHL-HIF axis is essential for ILC2 maturation and function via inhibition of glycolysis and induction of IL-33 receptor expression. These findings have implications for identifying therapeutic targets for allergic diseases. (Source: Immunity)
Source: Immunity - February 13, 2018 Category: Allergy & Immunology Authors: Qian Li, Dulei Li, Xian Zhang, Qingqing Wan, Wen Zhang, Mingke Zheng, Le Zou, Chris Elly, Jee H. Lee, Yun-Cai Liu Tags: Article Source Type: research

A Macrophage Colony-Stimulating Factor-Producing γδ T Cell Subset Prevents Malarial Parasitemic Recurrence
γδ T cell frequency increases late during mouse and human malaria. Mamedov et al. show that oligoclonal TRAV15N-1 (Vδ6.3) γδ T cells expand across various tissues and prevent late-stage parasitemic recurrence. These protective γδ T cells exhibit a distinct transcriptional profile that inc ludes abundantly expressed M-CSF, which protects against Plasmodium recurrence. (Source: Immunity)
Source: Immunity - February 6, 2018 Category: Allergy & Immunology Authors: Murad R. Mamedov, Anja Scholzen, Ramesh V. Nair, Katherine Cumnock, Justin A. Kenkel, Jose Henrique M. Oliveira, Damian L. Trujillo, Naresha Saligrama, Yue Zhang, Florian Rubelt, David S. Schneider, Yueh-hsiu Chien, Robert W. Sauerwein, Mark M. Davis Tags: Article Source Type: research

High-Dimensional Single-Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease
It has been challenging to map leukocytes in the brain, particularly during pathology. Mrdjen et  al. combine high-dimensional single-cell cytometry with fate mapping to capture the immune landscape of the brain. They identify different subsets of myeloid cells and the phenotypic changes in CNS immune cells during aging and in models of Alzheimer’s disease and multiple sclerosis. (Source: Immunity)
Source: Immunity - February 6, 2018 Category: Allergy & Immunology Authors: Dunja Mrdjen, Anto Pavlovic, Felix J. Hartmann, Bettina Schreiner, Sebastian G. Utz, Brian P. Leung, Iva Lelios, Frank L. Heppner, Jonathan Kipnis, Doron Merkler, Melanie Greter, Burkhard Becher Tags: Resource Source Type: research

Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4
Glucocorticoids have strong immunosuppressive effects, yet their physiological functions in the immune system remain unclear. Shimba et  al. demonstrate that glucocorticoids drive IL-7R expression in a diurnal fashion, which induces the redistribution of T cells between peripheral blood and lymphoid organs via CXCR4 expression and enhances adaptive immune responses. (Source: Immunity)
Source: Immunity - January 30, 2018 Category: Allergy & Immunology Authors: Akihiro Shimba, Guangwei Cui, Shizue Tani-ichi, Makoto Ogawa, Shinya Abe, Fumie Okazaki, Satsuki Kitano, Hitoshi Miyachi, Hisakata Yamada, Takahiro Hara, Yasunobu Yoshikai, Takashi Nagasawa, G ünther Schütz, Koichi Ikuta Tags: Article Source Type: research

B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells
Luo et  al. show that CD40 and BCR signaling in GC B cells is rewired to control very different pathways, and both signals are required for optimal induction of c-Myc, suggesting a mechanism of signaling-directed positive selection of GC B cells. (Source: Immunity)
Source: Immunity - January 30, 2018 Category: Allergy & Immunology Authors: Wei Luo, Florian Weisel, Mark J. Shlomchik Tags: Article Source Type: research

Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity
The mechanisms by which IL-10 facilitates the establishment of chronic infections are not fully understood. Smith et  al. demonstrate that during chronic infections, IL-10 upregulates N-glycan branching on CD8+ T cell surface glycoproteins, which reduces signal transduction downstream of the T cell receptor and decreases CD8+ T cell antigen sensitivity and capacity to control pathogen burden. (Source: Immunity)
Source: Immunity - January 23, 2018 Category: Allergy & Immunology Authors: Logan K. Smith, Giselle M. Boukhaled, Stephanie A. Condotta, Sabrina Mazouz, Jenna J. Guthmiller, Rahul Vijay, Noah S. Butler, Julie Bruneau, Naglaa H. Shoukry, Connie M. Krawczyk, Martin J. Richer Tags: Article Source Type: research

Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation
An increased understanding of infant antibody responses to RSV infection would greatly facilitate vaccine development. Goodwin et  al. isolate and structurally characterize antibodies from RSV-infected infants and identify potent neutralizing antibodies that lack somatic hypermutation. The results provide a framework for the rational design of age-specific RSV vaccines. (Source: Immunity)
Source: Immunity - January 23, 2018 Category: Allergy & Immunology Authors: Eileen Goodwin, Morgan S.A. Gilman, Daniel Wrapp, Man Chen, Joan O. Ngwuta, Syed M. Moin, Patricia Bai, Arvind Sivasubramanian, Ruth I. Connor, Peter F. Wright, Barney S. Graham, Jason S. McLellan, Laura M. Walker Tags: Article Source Type: research

NKp46 Receptor-Mediated Interferon- γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis
NK cells defend against various pathogens and tumors, but the mechanisms by which they control tumor metastases are not clear. Here, Glasner et  al. show that NK cells prevent tumor metastases in vivo by editing tumor architecture via NKp46-mediated IFN-γ production that leads to upregulation of extracellular matrix protein FN1 in the tumor. (Source: Immunity)
Source: Immunity - January 9, 2018 Category: Allergy & Immunology Authors: Ariella Glasner, Assi Levi, Jonatan Enk, Batya Isaacson, Sergey Viukov, Shari Orlanski, Alon Scope, Tzahi Neuman, Claes D. Enk, Jacob H. Hanna, Veronika Sexl, Stipan Jonjic, Barbara Seliger, Laurence Zitvogel, Ofer Mandelboim Tags: Article Source Type: research

Innate-like Cytotoxic Function of Bystander-Activated CD8+ T Cells Is Associated with Liver Injury in Acute Hepatitis A
During acute hepatitis A, hepatitis A virus (HAV)-infected cells produce IL-15 that induces TCR-independent bystander activation of non-HAV-specific memory CD8+ T  cells. These CD8+ T cells exert innate-like cytotoxicity triggered by NKG2D and NKp30 without TCR engagement. The severity of liver injury is associated with activation and innate-like cytotoxicity of non-HAV-specific CD8+ T cells, but not the activation of HAV-specific T cells. Thus, IL-15-ind uced bystander-activated CD8+ T cells are implicated in host injury during acute viral infection. (Source: Immunity)
Source: Immunity - January 2, 2018 Category: Allergy & Immunology Authors: Jihye Kim, Dong-Yeop Chang, Hyun Woong Lee, Hoyoung Lee, Jong Hoon Kim, Pil Soo Sung, Kyung Hwan Kim, Seon-Hui Hong, Wonseok Kang, Jino Lee, So Youn Shin, Hee Tae Yu, Sooseong You, Yoon Seok Choi, Insoo Oh, Dong Ho Lee, Dong Hyeon Lee, Min Kyung Jung, Kyu Tags: Article Source Type: research

Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens
It is not clear how precursor frequencies and antigen affinities impact interclonal B  cell competition. Abbott et al. show these parameters interdependently limit germinal center B cell fitness. When these variables are matched to the human physiological range, HIV bnAb precursor B cells compete in germinal centers, undergo extensive mutation, and form memory. (Source: Immunity)
Source: Immunity - December 26, 2017 Category: Allergy & Immunology Authors: Robert K. Abbott, Jeong Hyun Lee, Sergey Menis, Patrick Skog, Meghan Rossi, Takayuki Ota, Daniel W. Kulp, Deepika Bhullar, Oleksandr Kalyuzhniy, Colin Havenar-Daughton, William R. Schief, David Nemazee, Shane Crotty Tags: Article Source Type: research