Simultaneous Loss of Both Atypical Protein Kinase C Genes in the Intestinal Epithelium Drives Serrated Intestinal Cancer by Impairing Immunosurveillance
Serrated adenocarcinomas are an aggressive and treatment-resistant form of colorectal cancer. Nakanishi et  al. show that expression of atypical PKCs is reduced in human serrated tumors and that their loss results in spontaneous serrated tumorigenesis with stromal activation and immunosuppression in mice. The simultaneous inhibition of stromal activation combined with anti-PD-L1 showed synergistic thera peutic potential. (Source: Immunity)
Source: Immunity - December 11, 2018 Category: Allergy & Immunology Authors: Yuki Nakanishi, Angeles Duran, Antoine L ’Hermitte, Phillip M. Shelton, Naoko Nakanishi, Miguel Reina-Campos, Jianfeng Huang, Ferran Soldevila, Bas J.G. Baaten, Daniele V.F. Tauriello, Elias A. Castilla, Munveer S. Bhangoo, Fei Bao, Darren Sigal, Maria Tags: Article Source Type: research

Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN- γ and IL-12
Anti-PD-1 mAbs can induce sustained clinical responses in cancer but how they function in  vivo remains incompletely understood. Garris et al. show that effective anti-PD-1 immunotherapy requires intratumoral dendritic cells (DCs) producing IL-12. Anti-PD-1 indirectly activates DCs through IFN-γ released from drug-activated T cells. Furthermore, agonizing the non-canonical NF-κB pat hway activates DCs and enhances aPD-1 therapy in an IL-12-dependent manner. (Source: Immunity)
Source: Immunity - December 11, 2018 Category: Allergy & Immunology Authors: Christopher S. Garris, Sean P. Arlauckas, Rainer H. Kohler, Marcel P. Trefny, Seth Garren, C écile Piot, Camilla Engblom, Christina Pfirschke, Marie Siwicki, Jeremy Gungabeesoon, Gordon J. Freeman, Sarah E. Warren, SuFey Ong, Erica Browning, Christopher Tags: Article Source Type: research

Salmonella Persist in Activated Macrophages in T Cell-Sparse Granulomas but Are Contained by Surrounding CXCR3 Ligand-Positioned Th1 Cells
The pathogen Salmonella enterica (Se) can paradoxically persist in hosts while being controlled by IFN- γ-producing Th1 cells. Goldberg et al. show that the bacteria survive by resisting the effects of toxic host molecules in myeloid cells within granulomas, in areas lacking T cells. Infection is constrained by Th1 cells positioned around the granuloma via the CXCR3-CXCL9/10 chemokine axis. (Source: Immunity)
Source: Immunity - December 11, 2018 Category: Allergy & Immunology Authors: Michael F. Goldberg, Elizabeth K. Roeske, Lauren N. Ward, Thomas Pengo, Thamotharampillai Dileepan, Dmitri I. Kotov, Marc K. Jenkins Tags: Article Source Type: research

Microbiota-Induced TNF-like Ligand 1A Drives Group 3 Innate Lymphoid Cell-Mediated Barrier Protection and Intestinal T Cell Activation during Colitis
Inflammatory bowel disease (IBD) results from a dysregulated interaction between the microbiota and a genetically susceptible host. Castellanos et  al. show a protective role for microbial induction of the IBD-linked protein TL1A in promoting ILC3 barrier immunity and uncover a pathogenic role for TL1A-induced expression of OX40L on ILC3s in driving chronic T cell colitis. (Source: Immunity)
Source: Immunity - December 11, 2018 Category: Allergy & Immunology Authors: Jim G. Castellanos, Viola Woo, Monica Viladomiu, Gregory Putzel, Svetlana Lima, Gretchen E. Diehl, Andrew R. Marderstein, Jorge Gandara, Alexendar R. Perez, David R. Withers, Stephan R. Targan, David Q. Shih, Ellen J. Scherl, Randy S. Longman Tags: Article Source Type: research

Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier
Understanding how HIV-1 VRC01-class broadly neutralizing antibodies overcome maturation barriers is key for vaccine development. Bonsignori et  al. inferred the unmutated common ancestor of the VRC01 lineage, reconstructed the stages of lineage maturation, and identified multiple solutions adopted by evolving B cells to overcome the N276 glycan barrier and achieve broad neutralization. (Source: Immunity)
Source: Immunity - December 11, 2018 Category: Allergy & Immunology Authors: Mattia Bonsignori, Eric Scott, Kevin Wiehe, David Easterhoff, S. Munir Alam, Kwan-Ki Hwang, Melissa Cooper, Shi-Mao Xia, Ruijun Zhang, David C. Montefiori, Rory Henderson, Xiaoyan Nie, Garnett Kelsoe, M. Anthony Moody, Xuejun Chen, M. Gordon Joyce, Peter Tags: Article Source Type: research

Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers
Vaccine-induced immunity to HIV is a major research focus, but relevant correlates of protection remain controversial. Here, Pauthner et  al. study protection from hard-to-neutralize SHIVBG505 challenge after immunization with native-like BG505 Envelope trimers in nonhuman primates and identify neutralizing antibodies, but not T cell or ADCC activity, as correlates of protection. (Source: Immunity)
Source: Immunity - December 11, 2018 Category: Allergy & Immunology Authors: Matthias G. Pauthner, Joseph P. Nkolola, Colin Havenar-Daughton, Ben Murrell, Samantha M. Reiss, Raiza Bastidas, J érémie Prévost, Rebecca Nedellec, Benjamin von Bredow, Peter Abbink, Christopher A. Cottrell, Daniel W. Kulp, Talar Tokatlian, Bartek Nog Tags: Article Source Type: research

Circadian Expression of Migratory Factors Establishes Lineage-Specific Signatures that Guide the Homing of Leukocyte Subsets to Tissues
Leukocytes continuously circulate throughout the body. He et  al. demonstrate that trafficking patterns of major leukocyte subsets occur in a rhythmic manner dependent on the time-of-day-dependent expression of lineage- and tissue-specific factors. This influences the inflammatory response and leukemic tumor burden and translates to the migration behavior of human primary lymphocytes. (Source: Immunity)
Source: Immunity - December 4, 2018 Category: Allergy & Immunology Authors: Wenyan He, Stephan Holtkamp, Sophia Martina Hergenhan, Kerstin Kraus, Alba de Juan, Jasmin Weber, Paul Bradfield, Julien Martin Pierre Grenier, Jeoffrey Pelletier, David Druzd, Chien-Sin Chen, Louise Madeleine Ince, Susanne Bierschenk, Robert Pick, Markus Tags: Resource Source Type: research

Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes
Hammond et  al. redefine mouse microglia states using single-cell RNA-seq and in situ brain mapping. They find that microglia are most diverse in the developing, aged, and injured brain. Using focal demyelination, they show that microglia activation states are transcriptionally and spatially distinct within t he lesion environment. (Source: Immunity)
Source: Immunity - November 21, 2018 Category: Allergy & Immunology Authors: Timothy R. Hammond, Connor Dufort, Lasse Dissing-Olesen, Stefanie Giera, Adam Young, Alec Wysoker, Alec J. Walker, Frederick Gergits, Michael Segel, James Nemesh, Samuel E. Marsh, Arpiar Saunders, Evan Macosko, Florent Ginhoux, Jinmiao Chen, Robin J.M. Fr Tags: Resource Source Type: research

RAS P21 Protein Activator 3 (RASA3) Specifically Promotes Pathogenic T Helper 17 Cell Generation by Repressing T Helper 2 Cell-Biased Programs
Pathogenic Th17 cells promote immune pathology, but how their generation is controlled remains largely unknown. Wu et  al. reveal that RASA3 is essential for pathogenic Th17 cell generation but dispensable for non-pathogenic Th17 cell generation. RASA3 functions by repressing Th2 cell programs in pathogenic Th17 cells by fine-tuning IRF4 protein expression. (Source: Immunity)
Source: Immunity - November 13, 2018 Category: Allergy & Immunology Authors: Bing Wu, Song Zhang, Zengli Guo, Gang Wang, Ge Zhang, Ling Xie, Jitong Lou, Xian Chen, Di Wu, Wolfgang Bergmeier, Junnian Zheng, Yisong Y. Wan Tags: Article Source Type: research

Antibodies to Costimulatory Receptor 4-1BB Enhance Anti-tumor Immunity via T Regulatory Cell Depletion and Promotion of CD8  T Cell Effector Function
Buchan et  al. reveal dual anti-tumor activities for antibodies to the co-stimulatory receptor 4-1BB, which depend on antibody isotype and FcγR availability. Sequential scheduling of anti-4-1BB and checkpoint blockade mAbs, and antibodies engineered to harness both Treg cell depleting and effector cell agon ism properties show potent anti-tumor activity in preclinical models, laying the groundwork for translation into the clinic. (Source: Immunity)
Source: Immunity - November 13, 2018 Category: Allergy & Immunology Authors: Sarah L. Buchan, Lang Dou, Marcus Remer, Steven G. Booth, Stuart N. Dunn, Chester Lai, Monika Semmrich, Ingrid Teige, Linda M årtensson, Christine A. Penfold, H.T. Claude Chan, Jane E. Willoughby, C. Ian Mockridge, Lekh N. Dahal, Kirstie L.S. Cleary, Son Tags: Article Source Type: research

Aryl Hydrocarbon Receptor Signaling Cell Intrinsically Inhibits Intestinal Group 2 Innate Lymphoid Cell Function
The aryl hydrocarbon receptor (Ahr) promotes ILC3 maintenance and function. Li et  al. report that Ahr restricts intestinal ILC2 function in a cell-intrinsic manner, suggesting a central role for gut adaptation of Ahr expression in regulating the ILC2-ILC3 balance. (Source: Immunity)
Source: Immunity - November 13, 2018 Category: Allergy & Immunology Authors: Shiyang Li, John W. Bostick, Jian Ye, Ju Qiu, Bin Zhang, Joseph F. Urban, Dorina Avram, Liang Zhou Tags: Article Source Type: research

Microbiota-Derived Lactate Activates Production of Reactive Oxygen Species by the Intestinal NADPH Oxidase Nox and Shortens Drosophila Lifespan
Iatsenko et  al. find that flies bearing a mutation in a peptidoglycan recognition protein exhibit dysbiosis and shortened lifespan. In these flies, the unrestricted growth of a commensal bacterium generates excessive lactate, which triggers ROS production in intestinal cells and subsequent dysplasia. This ROS -producing pathway is conserved, suggesting relevance of such host-microbe metabolic crosstalk in age-related pathologies in humans. (Source: Immunity)
Source: Immunity - November 13, 2018 Category: Allergy & Immunology Authors: Igor Iatsenko, Jean-Philippe Boquete, Bruno Lemaitre Tags: Article Source Type: research

Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis
Girbl et  al. find that sequential interactions with the chemokines CXCL1 and CXCL2 guide neutrophil crawling and subsequent migration through venular walls during inflammation. Transmigrating neutrophils promoted unidirectional luminal-to-abluminal migration by depositing CXCL2 on the chemokine receptor AC KR1 at endothelial junctions, providing a paradigm of self-guided migration. (Source: Immunity)
Source: Immunity - November 13, 2018 Category: Allergy & Immunology Authors: Tamara Girbl, Tchern Lenn, Lorena Perez, Lo ïc Rolas, Anna Barkaway, Aude Thiriot, Carlos del Fresno, Eleanor Lynam, Elin Hub, Marcus Thelen, Gerard Graham, Ronen Alon, David Sancho, Ulrich H. von Andrian, Mathieu-Benoit Voisin, Antal Rot, Sussan Noursha Tags: Article Source Type: research

The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression
Tyagi et  al. show that oral supplementation with the widely used probiotic, Lactobacillus rhamnosus GG (LGG), increases bone mass in mice by increasing the serum levels of the short chain fatty acid butyrate. LGG or butyrate increase the frequency of regulatory T (Treg) cells in the intestine and in the bo ne marrow. Treg cells stimulate CD8+ T cells to secrete the Wnt ligand Wnt10b, which stimulates bone formation by activating Wnt signaling in osteoblasts. Therefore, LGG and butyrate may represent new interventions for the prevention and treatment of osteoporosis. (Source: Immunity)
Source: Immunity - November 13, 2018 Category: Allergy & Immunology Authors: Abdul Malik Tyagi, Mingcan Yu, Trevor M. Darby, Chiara Vaccaro, Jau-Yi Li, Joshua A. Owens, Emory Hsu, Jonathan Adams, M. Neale Weitzmann, Rheinallt M. Jones, Roberto Pacifici Tags: Article Source Type: research

Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance
An unresolved problem in organ transplantation is to establish graft acceptance in the absence of long-term immunosuppressive therapy. Braza et  al. unravel important molecular mechanisms underlying myeloid cell activation in an experimental organ transplantation model and develop a combined nanoimmunotherapy that targets myeloid cells in hematopoietic organs and the allograft. Short-term nanobiologic immunotherapy prevents inflammation an d induces indefinite allograft survival. (Source: Immunity)
Source: Immunity - November 6, 2018 Category: Allergy & Immunology Authors: Mounia S. Braza, Mandy M.T. van Leent, Marnix Lameijer, Brenda L. Sanchez-Gaytan, Rob J.W. Arts, Carlos P érez-Medina, Patricia Conde, Mercedes R. Garcia, Maria Gonzalez-Perez, Manisha Brahmachary, Francois Fay, Ewelina Kluza, Susanne Kossatz, Regine J. Tags: Report Source Type: research

High-Dimensional Single-Cell Analysis Identifies Organ-Specific Signatures and Conserved NK Cell Subsets in Humans and Mice
Several NK cell subsets have been reported in humans and mice, but their heterogeneity remains poorly characterized. Using high-throughput single-cell RNA-seq, Crinier et  al. provide conserved tissue-specific gene signatures of NK cells from spleen and blood and identified two major NK cell subsets transcriptionally similar across organs and species. (Source: Immunity)
Source: Immunity - November 6, 2018 Category: Allergy & Immunology Authors: Adeline Crinier, Pierre Milpied, Bertrand Escali ère, Christelle Piperoglou, Justine Galluso, Anaïs Balsamo, Lionel Spinelli, Inaki Cervera-Marzal, Mikaël Ebbo, Mathilde Girard-Madoux, Sébastien Jaeger, Emilie Bollon, Sami Hamed, Jean Hardwigsen, Soph Tags: Resource Source Type: research

Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R −STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity
Treg cells respond to low IL-2 levels, but how STAT5 is activated under these conditions remains uncertain. Shi et  al. demonstrate that the serine/threonine kinases Mst1 and Mst2 sense IL-2 signals to promote STAT5 activation to maintain Treg cell homeostasis, lineage stability, and the highly suppressive phosphorylated-STAT5+ Treg cell subpopulation. Therefore, a non-canonical Hippo pathway orchestrates IL-2− STAT5 signaling selectively in Treg cells. (Source: Immunity)
Source: Immunity - November 6, 2018 Category: Allergy & Immunology Authors: Hao Shi, Chaohong Liu, Haiyan Tan, Yuxin Li, Thanh-Long M. Nguyen, Yogesh Dhungana, Cliff Guy, Peter Vogel, Geoffrey Neale, Sherri Rankin, Yongqiang Feng, Junmin Peng, Wufan Tao, Hongbo Chi Tags: Article Source Type: research

Interleukin-17 Producing γδ T Cells Originate from SOX13+ Progenitors that Are Independent of γδTCR Signaling
The role of TCR in establishing IL-17 producing γδ T (Tγδ17) cell lineage identity during thymic development remains controversial. Spidale et al. identify a Sox13hi progenitor to Vγ2+ Tγδ17 cells and demonstrate that progenitor programming is dependent on SOX13 and TCF7 but independent of γδTCR. (Source: Immunity)
Source: Immunity - November 6, 2018 Category: Allergy & Immunology Authors: Nicholas A. Spidale, Katelyn Sylvia, Kavitha Narayan, Bing Miu, Michela Frascoli, Heather J. Melichar, Wu Zhihao, Jan Kisielow, Amy Palin, Thomas Serwold, Paul Love, Michihiro Kobayashi, Momoko Yoshimoto, Nitya Jain, Joonsoo Kang Tags: Article Source Type: research

The T Cell Antigen Receptor α Transmembrane Domain Coordinates Triggering through Regulation of Bilayer Immersion and CD3 Subunit Associations
While TCR triggering is critical for adaptive immunity, how bioforces accompanying ligand binding transduce signals through the cell membrane is unknown. Brazin et  al. define dynamic structural movements within the TCRα transmembrane domain linked to fundamental TCR complex mechanobiology, including subunit topological rearrangements that foster dissociation of CD3 dimers and cell activation. (Source: Immunity)
Source: Immunity - October 30, 2018 Category: Allergy & Immunology Authors: Kristine N. Brazin, Robert J. Mallis, Andras Boeszoermenyi, Yinnian Feng, Akihiro Yoshizawa, Pedro A. Reche, Pavanjeet Kaur, Kevin Bi, Rebecca E. Hussey, Jonathan S. Duke-Cohan, Likai Song, Gerhard Wagner, Haribabu Arthanari, Matthew J. Lang, Ellis L. Rei Tags: Article Source Type: research

An Interleukin-23-Interleukin-22 Axis Regulates Intestinal Microbial Homeostasis to Protect from Diet-Induced Atherosclerosis
While anti-cytokine therapies show promising results in autoimmune diseases, its effects on cardiovascular disease development are not well understood. Fatkhullina and colleagues show that inactivation of IL-23-IL-22 signaling leads to deterioration of the intestinal barrier, expansion of pro-atherogenic bacteria, and production of metabolites promoting macrophage activation and atherosclerosis. (Source: Immunity)
Source: Immunity - October 30, 2018 Category: Allergy & Immunology Authors: Aliia R. Fatkhullina, Iuliia O. Peshkova, Amiran Dzutsev, Turan Aghayev, John A. McCulloch, Vishal Thovarai, Jonathan H. Badger, Ravi Vats, Prithu Sundd, Hsin-Yao Tang, Andrew V. Kossenkov, Stanley L. Hazen, Giorgio Trinchieri, Sergei I. Grivennikov, Ekat Tags: Article Source Type: research

Cholesterol Homeostatic Regulator SCAP-SREBP2 Integrates NLRP3 Inflammasome Activation and Cholesterol Biosynthetic Signaling in Macrophages
The metabolic-inflammatory crosstalk plays a key role in host defense against pathogens and inflammation. Guo and colleagues demonstrate that SCAP-SREBP2 complex integrates NLRP3 inflammasome activation and cholesterol biosynthetic signaling during inflammation. (Source: Immunity)
Source: Immunity - October 23, 2018 Category: Allergy & Immunology Authors: Chuansheng Guo, Zhexu Chi, Danlu Jiang, Ting Xu, Weiwei Yu, Zhen Wang, Sheng Chen, Li Zhang, Qianyun Liu, Xingchen Guo, Xue Zhang, Wenxin Li, Linrong Lu, Yingliang Wu, Bao-Liang Song, Di Wang Tags: Article Source Type: research

T Cell-Intrinsic Receptor Interacting Protein 2 Regulates Pathogenic T Helper 17 Cell Differentiation
RIP2 is the key adaptor molecule for NOD1- and NOD2-mediated intracellular signaling to sense pathogens and cell activation in myeloid cells. Shimada, Porritt, and colleagues demonstrate a previously unappreciated role for RIP2 in Th17 cell regulation and differentiation in a T  cell-intrinsic manner. (Source: Immunity)
Source: Immunity - October 23, 2018 Category: Allergy & Immunology Authors: Kenichi Shimada, Rebecca A. Porritt, Janet L. Markman, Jacqueline Gire O ’Rourke, Daiko Wakita, Magali Noval Rivas, Chihiro Ogawa, Lina Kozhaya, Gislâine A. Martins, Derya Unutmaz, Robert H. Baloh, Timothy R. Crother, Shuang Chen, Moshe Arditi Tags: Article Source Type: research

CD8+ T Cell Priming in Established Chronic Viral Infection Preferentially Directs Differentiation of Memory-like Cells for Sustained Immunity
How new T  cell responses are mounted during chronic infection is unclear. Snell et al. demonstrate that unlike T cells primed at the onset of infection, CD8+ T cells primed after chronic viral infection is established are differentially programmed into less exhausted, TCF1+ memory-like cells that respond better to immunotherapy but diminish immunity to cancers that arise in chronic infection. (Source: Immunity)
Source: Immunity - October 9, 2018 Category: Allergy & Immunology Authors: Laura M. Snell, Bethany L. MacLeod, Jaclyn C. Law, Ivan Osokine, Heidi J. Elsaesser, Kebria Hezaveh, Russell J. Dickson, Marc A. Gavin, Cynthia J. Guidos, Tracy L. McGaha, David G. Brooks Tags: Article Source Type: research

Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus
The role of extrafollicular B cells in human systemic lupus is unknown. Jenks et  al. define the main components of this pathway and its prominence in severe disease. Its activation is mediated by hyper-responsiveness to Toll-like receptor-7 and leads to the generation of autoreactive antibody-secreting plasmablasts. (Source: Immunity)
Source: Immunity - October 9, 2018 Category: Allergy & Immunology Authors: Scott A. Jenks, Kevin S. Cashman, Esther Zumaquero, Urko M. Marigorta, Aakash V. Patel, Xiaoqian Wang, Deepak Tomar, Matthew C. Woodruff, Zoe Simon, Regina Bugrovsky, Emily L. Blalock, Christopher D. Scharer, Christopher M. Tipton, Chungwen Wei, S. Sam Li Tags: Article Source Type: research

The Endotoxin Delivery Protein HMGB1 Mediates Caspase-11-Dependent Lethality in Sepsis
Caspase-11, a cytosolic LPS receptor, mediates endotoxic shock. Deng and colleagues demonstrate that hepatocyte-released HMGB1 mediates caspase-11-dependent pyroptosis and lethality in sepsis by delivering extracellular LPS into the cytosol of macrophages and endothelial cells, where LPS activates caspase-11. (Source: Immunity)
Source: Immunity - October 9, 2018 Category: Allergy & Immunology Authors: Meihong Deng, Yiting Tang, Wenbo Li, Xiangyu Wang, Rui Zhang, Xianying Zhang, Xin Zhao, Jian Liu, Cheng Tang, Zhonghua Liu, Yongzhuo Huang, Huige Peng, Lehui Xiao, Daolin Tang, Melanie J. Scott, Qingde Wang, Jing Liu, Xianzhong Xiao, Simon Watkins, Jianhu Tags: Article Source Type: research

The Majority of CD45 – Ter119– CD31– Bone Marrow Cell Fraction Is of Hematopoietic Origin and Contains Erythroid and Lymphoid Progenitors
Bone marrow triple-negative CD45 – Ter119– CD31– cells are thought to contain heterogeneous stromal cell populations. Boulais et al. show these cells are mostly hematopoietic in origin and contain previously unappreciated stromal-associated erythroid and B-lymphoid progenitor populations. (Source: Immunity)
Source: Immunity - October 9, 2018 Category: Allergy & Immunology Authors: Philip E. Boulais, Toshihide Mizoguchi, Samuel Zimmerman, Fumio Nakahara, Judith Vivi é, Jessica C. Mar, Alexander van Oudenaarden, Paul S. Frenette Tags: Article Source Type: research

Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution
Regulatory T  cells suppress inflammation and promote tissue repair in multiple contexts. Proto, Doran, et al. show that Treg cells enhance the ability of macrophages to engulf apoptotic cells (efferocytosis) and thereby promote resolution of inflammation. (Source: Immunity)
Source: Immunity - October 2, 2018 Category: Allergy & Immunology Authors: Jonathan D. Proto, Amanda C. Doran, Galina Gusarova, Arif Yurdagul, Erdi Sozen, Manikandan Subramanian, Mohammad N. Islam, Christina C. Rymond, Jasper Du, Jaime Hook, George Kuriakose, Jahar Bhattacharya, Ira Tabas Tags: Article Source Type: research

B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen
Initiation of CD4+ T  cell response depends on antigen-presenting cells. Contrary to the paradigm that dendritic cells are required for this process, Hong et al. show that antigen-specific B cells are essential and sufficient to activate naive CD4+ T cells in response to virus-like particles or influenza vaccination. (Source: Immunity)
Source: Immunity - October 2, 2018 Category: Allergy & Immunology Authors: Sheng Hong, Zhimin Zhang, Hongtao Liu, Meijie Tian, Xiping Zhu, Zhuqiang Zhang, Weihong Wang, Xuyu Zhou, Fuping Zhang, Qing Ge, Bing Zhu, Hong Tang, Zhaolin Hua, Baidong Hou Tags: Article Source Type: research

Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44
The function of IgD has been mysterious. Shan et  al. find that IgD recognized food antigens and targeted basophils through galectin-9. IgD ligation by antigen induced basophil secretion of IL-4, IL-5, and IL-13, which amplified Th2 cell-mediated IgG1 and IgE production by B cells. IgD also constrained IgE-mediated basophil degranulation. (Source: Immunity)
Source: Immunity - October 2, 2018 Category: Allergy & Immunology Authors: Meimei Shan, Jorge Carrillo, Ada Yeste, Cindy Gutzeit, Daniel Segura-Garz ón, A. Cooper Walland, Marc Pybus, Emilie K. Grasset, John R. Yeiser, Dean B. Matthews, Willem van de Veen, Laura Comerma, Bing He, Tadech Boonpiyathad, Haekyung Lee, Julià Blanco Tags: Article Source Type: research

A Metabolism-Based Quorum Sensing Mechanism Contributes to Termination of Inflammatory Responses
Mechanisms sensing when a sufficient number of immune cells have accumulated in tissues to terminate inflammation are incompletely understood. Here, Postat et  al. establish that NO produced at inflammatory sites acts as a quorum sensing mechanism to adjust monocyte-derived cell respiration and cytokine production to their density in the tissue. (Source: Immunity)
Source: Immunity - September 25, 2018 Category: Allergy & Immunology Authors: J érémy Postat, Romain Olekhnovitch, Fabrice Lemaître, Philippe Bousso Tags: Article Source Type: research

PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes
Gawden-Bone et  al. show that during immune synapse formation, rapid depletion of PIP5K at the synapse triggers subsequent changes in membrane composition and actin dynamics to establish a zone of localized granule secretion. (Source: Immunity)
Source: Immunity - September 11, 2018 Category: Allergy & Immunology Authors: Christian M. Gawden-Bone, Gordon L. Frazer, Arianne C. Richard, Claire Y. Ma, Katharina Strege, Gillian M. Griffiths Tags: Article Source Type: research

Antibodies Set Boundaries Limiting Microbial Metabolite Penetration and the Resultant Mammalian Host Response
Bacteria-derived metabolites pervade the mammalian host, shaping immunity and metabolism. Using stable isotope tracing, Uchimura and colleagues profile the scope and depth of host tissue penetration by bacterial metabolites. Extensive host immune and metabolic responses to microbial metabolite penetration are constrained by secretory antibodies that limit microbial small-intestinal dwell time. (Source: Immunity)
Source: Immunity - September 4, 2018 Category: Allergy & Immunology Authors: Yasuhiro Uchimura, Tobias Fuhrer, Hai Li, Melissa A. Lawson, Michael Zimmermann, Bahtiyar Yilmaz, Joel Zindel, Francesca Ronchi, Marcel Sorribas, Siegfried Hapfelmeier, Stephanie C. Ganal-Vonarburg, Mercedes Gomez de Ag üero, Kathy D. McCoy, Uwe Sauer, A Tags: Article Source Type: research

CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway
Human innate lymphoid cells (ILCs) develop from tissue-resident ILC precursors (ILCPs) in secondary lymphoid tissues. Here, Chen et  al. describe a model of human ILC development in tonsils in which NK cells and group 3 ILCs derive from a CD56+ subset of ILCPs that cannot differentiate into group 2 ILCs. (Source: Immunity)
Source: Immunity - September 4, 2018 Category: Allergy & Immunology Authors: Luxi Chen, Youssef Youssef, Cameron Robinson, Gabrielle F. Ernst, Mary Y. Carson, Karen A. Young, Steven D. Scoville, Xiaoli Zhang, Regine Harris, Palak Sekhri, Anthony G. Mansour, Wing K. Chan, Ansel P. Nalin, Hsiaoyin C. Mao, Tiffany Hughes, Emily M. Ma Tags: Article Source Type: research

The Zinc-Finger Protein ZCCHC3 Binds RNA and Facilitates Viral RNA Sensing and Activation of the RIG-I-like Receptors
Recognition of viral RNA by RIG-I-like receptors (RLRs) initiates innate antiviral response. Lian et  al. demonstrate that ZCCHC3 is a co-receptor for RLRs, thereby acting as an important modulator of innate antiviral response. (Source: Immunity)
Source: Immunity - September 4, 2018 Category: Allergy & Immunology Authors: Huan Lian, Ru Zang, Jin Wei, Wen Ye, Ming-Ming Hu, Yun-Da Chen, Xia-Nan Zhang, Yi Guo, Cao-Qi Lei, Qing Yang, Wei-Wei Luo, Shu Li, Hong-Bing Shu Tags: Article Source Type: research

Gasdermin D Restrains Type I Interferon Response to Cytosolic DNA by Disrupting Ionic Homeostasis
Gasdermin D is a pore-forming protein, which upon activation by inflammasome complexes mediates pyroptotic cell death and IL-1 release. Banerjee et  al. demonstrate a previously unknown regulatory role for gasdermin D-driven K+ efflux in reining in cGAS-dependent type I interferon response to cytosolic DNA. (Source: Immunity)
Source: Immunity - August 28, 2018 Category: Allergy & Immunology Authors: Ishita Banerjee, Bharat Behl, Morena Mendonca, Gaurav Shrivastava, Ashley J. Russo, Antoine Menoret, Arundhati Ghosh, Anthony T. Vella, Sivapriya Kailasan Vanaja, Saumendra N. Sarkar, Katherine A. Fitzgerald, Vijay A.K. Rathinam Tags: Article Source Type: research

Non-canonical NF- κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy
It is known that the NF- κB pathway plays a crucial role in supporting tumor initiation, progression, and the radioresistance of tumor cells. Hou et al. demonstrate that the deficiency of non-canonical NF-κB, but not canonical NF-κB, promotes radiation-induced anti-tumor immunity by regulating the STING-mediated type I IFN expression. (Source: Immunity)
Source: Immunity - August 28, 2018 Category: Allergy & Immunology Authors: Yuzhu Hou, Hua Liang, Enyu Rao, Wenxin Zheng, Xiaona Huang, Liufu Deng, Yuan Zhang, Xinshuang Yu, Meng Xu, Helena Mauceri, Ainhoa Arina, Ralph R. Weichselbaum, Yang-Xin Fu Tags: Article Source Type: research

Lung γδ T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity
Influenza infection causes mortality in infants and protective immunity in this population is poorly understood. Guo et  al. find that γδ T cells are required for recovery after neonatal influenza infection. γδ T cell-derived IL-17A is associated with the tissue repair response orchestrated by IL-33, ILC2s, and amphiregulin, and IL-17A correlates with improved disease outcomes in influenza-infected children. (Source: Immunity)
Source: Immunity - August 28, 2018 Category: Allergy & Immunology Authors: Xi-zhi J. Guo, Pradyot Dash, Jeremy Chase Crawford, E. Kaitlynn Allen, Anthony E. Zamora, David F. Boyd, Susu Duan, Resha Bajracharya, Walid A. Awad, Nopporn Apiwattanakul, Peter Vogel, Thirumala-Devi Kanneganti, Paul G. Thomas Tags: Article Source Type: research

The Chemokine Receptor CCR8 Promotes the Migration of Dendritic Cells into the Lymph Node Parenchyma to Initiate the Allergic Immune Response
Migration of dendritic cells (DCs) into the lymph node (LN) initiates adaptive immunity and is thought to be solely dependent on CCR7. Sokol et  al. show that in a cutaneous type 2 immune response, CCR8 synergizes with CCR7 and is necessary to promote the entry of allergen-activated DCs into the LN parenchyma, which is required for Th2 differentiation. (Source: Immunity)
Source: Immunity - August 28, 2018 Category: Allergy & Immunology Authors: Caroline L. Sokol, Ryan B. Camire, Michael C. Jones, Andrew D. Luster Tags: Article Source Type: research

A Map of Toll-like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type-Specific, and Temporal Patterns
Price et  al. generate five strains of reporter mice to visualize the expression of individual TLRs on intestinal epithelial cells (IECs). Their findings reveal unexpected diversity in the temporal and spatial patterns of TLR expression and in the responsiveness of IECs to microbial stimuli. (Source: Immunity)
Source: Immunity - August 28, 2018 Category: Allergy & Immunology Authors: April E. Price, Kiarash Shamardani, Kyler A. Lugo, Jacques Deguine, Allison W. Roberts, Bettina L. Lee, Gregory M. Barton Tags: Resource Source Type: research

The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining Intestinal Stem Cell Homeostasis and Barrier Integrity
Metidji et  al. show that deletion of Ahr in intestinal epithelial cells results in a defective barrier and unrestricted proliferation of intestinal stem cells (ISCs), culminating in malignant transformation. Activation of AHR by dietary ligands guards the ISC niche and maintains intestinal barrier homeostasi s. (Source: Immunity)
Source: Immunity - August 14, 2018 Category: Allergy & Immunology Authors: Amina Metidji, Sara Omenetti, Stefania Crotta, Ying Li, Emma Nye, Ellie Ross, Vivian Li, Muralidhara R. Maradana, Chris Schiering, Brigitta Stockinger Tags: Article Source Type: research

The Kinase IKK β Regulates a STING- and NF-κB-Dependent Antiviral Response Pathway in Drosophila
Goto et  al. show that the kinase dIKKβ and the NF-κB factor Relish control replication of picorna-like viruses in flies through induction of antiviral genes, including a homolog of STING. A STING-IKKβ-NF-κB cassette participates in resistance to picorna-like viruses, pointing to an evolutionarily anci ent role of STING in antiviral immunity. (Source: Immunity)
Source: Immunity - August 14, 2018 Category: Allergy & Immunology Authors: Akira Goto, Kiyoshi Okado, Nelson Martins, Hua Cai, Vincent Barbier, Olivier Lamiable, Laurent Troxler, Estelle Santiago, Lauriane Kuhn, Donggi Paik, Neal Silverman, Andreas Holleufer, Rune Hartmann, Jiyong Liu, Tao Peng, Jules A. Hoffmann, Carine Meignin Tags: Article Source Type: research

LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis
Treg cells control of tissue resident macrophages and ILC3 function has not been elucidated. Bauche et  al. demonstrate that LAG-3+ Treg cells suppress the production of pro-inflammatory cytokines by CX3CR1+ macrophages and thereby inhibit ILC3-driven colitis. (Source: Immunity)
Source: Immunity - August 7, 2018 Category: Allergy & Immunology Authors: David Bauch é, Barbara Joyce-Shaikh, Renu Jain, Jeff Grein, Karin S. Ku, Wendy M. Blumenschein, Stephanie C. Ganal-Vonarburg, Douglas C. Wilson, Terrill K. McClanahan, Rene de Waal Malefyt, Andrew J. Macpherson, Lakshmanan Annamalai, Jennifer H. Yearley, Tags: Article Source Type: research

Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization
Comprehensive epitope mapping is fundamental to understanding immune responses. Bianchi et  al. applied electron microscopy to study polyclonal antibody responses in HIV-Env-immunized rabbits. Different antibody specificities were identified and followed over time, revealing the source of neutralization, a distinct class of antibodies, and a highly convergent structural evolution of the neutralizing antibodies. (Source: Immunity)
Source: Immunity - August 7, 2018 Category: Allergy & Immunology Authors: Matteo Bianchi, Hannah L. Turner, Bartek Nogal, Christopher A. Cottrell, David Oyen, Matthias Pauthner, Raiza Bastidas, Rebecca Nedellec, Laura E. McCoy, Ian A. Wilson, Dennis R. Burton, Andrew B. Ward, Lars Hangartner Tags: Article Source Type: research

PD-1 Controls Follicular T Helper Cell Positioning and Function
Tfh cells highly express the inhibitory PD-1 molecule, although its function in the germinal center response is not well understood. Shi et  al. show that, by operating in both costimulatory and bystander signaling mode, PD-1 suppresses follicular T cell recruitment but promotes Tfh cell concentration in the GC territory and helps maintain the stringency of GC affinity selection. (Source: Immunity)
Source: Immunity - July 31, 2018 Category: Allergy & Immunology Authors: Jingwen Shi, Shiyue Hou, Qian Fang, Xin Liu, Xiaolong Liu, Hai Qi Tags: Article Source Type: research

DEER Spectroscopy Measurements Reveal Multiple Conformations of HIV-1 SOSIP Envelopes that Show Similarities with Envelopes on Native Virions
HIV-1 Env, the only target of neutralizing antibodies, is highly dynamic, and only snapshots of static conformations are available. Stadtmueller et  al. used DEER spectroscopy to map conformations of soluble Env and its complexes with antibodies or the CD4 receptor. Results reveal similarities to virion-bound Env and buried non-neutralizing antibody epitopes, advancing knowledge of Env function and vaccine design. (Source: Immunity)
Source: Immunity - July 31, 2018 Category: Allergy & Immunology Authors: Beth M. Stadtmueller, Michael D. Bridges, Kim-Marie Dam, Michael T. Lerch, Kathryn E. Huey-Tubman, Wayne L. Hubbell, Pamela J. Bjorkman Tags: Article Source Type: research

The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages
Scott et  al. demonstrate that ZEB2 is critical for maintaining the tissue identities of macrophages. Loss of ZEB2 results in tissue-specific changes in different macrophage populations and their subsequent disappearance. In Kupffer cells, ZEB2 maintains LXRα expression, loss of which reproduces the change in Kupffer cell identity and their disappearance. (Source: Immunity)
Source: Immunity - July 31, 2018 Category: Allergy & Immunology Authors: Charlotte L. Scott, Wouter T ’Jonck, Liesbet Martens, Helena Todorov, Dorine Sichien, Bieke Soen, Johnny Bonnardel, Sofie De Prijck, Niels Vandamme, Robrecht Cannoodt, Wouter Saelens, Bavo Vanneste, Wendy Toussaint, Pieter De Bleser, Nozomi Takahashi, P Tags: Article Source Type: research

Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies
A substantial portion of the engineered HIV gp120 immunogen eOD-GT8-elicited antibodies target non-CD4 binding site (bs) epitopes, potentially limiting its efficacy. Duan et  al. used N-linked glycans to mask epitopes outside the CD4bs of eOD-GT8, leading to enhanced elicitation of CD4bs antibodies, including VRC01-class precursors, and reduced off-target antibody responses in a human VH1-2 mouse model. (Source: Immunity)
Source: Immunity - July 31, 2018 Category: Allergy & Immunology Authors: Hongying Duan, Xuejun Chen, Jeffrey C. Boyington, Cheng Cheng, Yi Zhang, Alexander J. Jafari, Tyler Stephens, Yaroslav Tsybovsky, Oleksandr Kalyuzhniy, Peng Zhao, Sergey Menis, Martha C. Nason, Erica Normandin, Maryam Mukhamedova, Brandon J. DeKosky, Lanc Tags: Article Source Type: research

PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells
Th1 cells are known for their enhanced stability, so mechanisms that mediate their flexibility are poorly studied. Here, Stathopoulou et  al. demonstrate that plasticity of Th1 cells to Tbet+iTreg cells is mediated by PD-1 signaling via asparaginyl endopeptidase (AEP). AEP inhibition enhanced iTreg cells in GvHD and tumor models. (Source: Immunity)
Source: Immunity - July 24, 2018 Category: Allergy & Immunology Authors: Chaido Stathopoulou, Arunakumar Gangaplara, Grace Mallett, Francis A. Flomerfelt, Lukasz P. Liniany, David Knight, Leigh A. Samsel, Rolando Berlinguer-Palmini, Joshua J. Yim, Tania C. Felizardo, Michael A. Eckhaus, Laura Edgington-Mitchell, Jonathan Marti Tags: Article Source Type: research

Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen
Macrophages are essential to maintain tissue homeostasis. Lim and colleagues demonstrate that perivascular LYVE-1-expressing macrophages prevent arterial stiffness by controlling the expression of collagen in vascular smooth muscle cells, a process dependent on the engagement of LYVE-1 with hyaluronan on smooth muscle cells. (Source: Immunity)
Source: Immunity - July 24, 2018 Category: Allergy & Immunology Authors: Hwee Ying Lim, Sheau Yng Lim, Chek Kun Tan, Chung Hwee Thiam, Chi Ching Goh, Daniel Carbajo, Samantha Hui Shang Chew, Peter See, Svetoslav Chakarov, Xiao Nong Wang, Li Hui Lim, Louise A. Johnson, Josephine Lum, Chui Yee Fong, Ariff Bongso, Arijit Biswas, Tags: Article Source Type: research

Airway Epithelial Cell-Derived Colony Stimulating Factor-1 Promotes Allergen Sensitization
Airway epithelial cells are the first line of defense against foreign antigens and influence the microenvironment of the lung by secreting bioactive mediators. Moon and colleagues demonstrate that airway epithelial cells regulate dendritic cells for trafficking aeroallergen and subsequent development of adaptive immune responses. (Source: Immunity)
Source: Immunity - July 24, 2018 Category: Allergy & Immunology Authors: Hyung-Geun Moon, Seung-jae Kim, Jong Jin Jeong, Seon-Sook Han, Nizar N. Jarjour, Hyun Lee, Sherry L. Abboud-Werner, Sangwoon Chung, Hak Soo Choi, Viswanathan Natarajan, Steven J. Ackerman, John W. Christman, Gye Young Park Tags: Article Source Type: research