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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

Structural Activation of Pro-inflammatory Human Cytokine IL-23 by Cognate IL-23 Receptor Enables Recruitment of the Shared Receptor IL-12R β1
IL-23, a human cytokine under intense clinical targeting, is pivotal to cellular responses underlying widespread inflammatory and autoimmune diseases, such as psoriasis and rheumatoid arthritis. Bloch et  al. determine the structure of IL-23 bound by one of its receptors, IL-23R, and reveal how IL-23R activates IL-23 for recruiting IL-12Rβ1 to the signaling assembly. Together with identifying an interaction hotspot, such findings may contribute to additional approaches for the mechanistic and ther apeutic interrogation of receptor complexes mediated by IL-12 family members. (Source: Immunity)
Source: Immunity - December 26, 2017 Category: Allergy & Immunology Authors: Yehudi Bloch, Laura Bouchareychas, Romain Merceron, Katarzyna Sk ładanowska, Lien Van den Bossche, Sammy Detry, Srinath Govindarajan, Dirk Elewaut, Filomeen Haerynck, Melissa Dullaers, Iannis E. Adamopoulos, Savvas N. Savvides Tags: Article Source Type: research

Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells
Essig et  al. show that spontaneous activation and aberrant differentiation of Roquin-deficient T cells involves cell-intrinsic causes in not only conventional T cells but also impaired Treg cell function. In both cell types, Roquin inhibits the PI3K-mTOR signaling pathway at several levels, thereby contr olling protein biosynthesis and limiting differentiation toward Th17 and Tfh cells as well as preventing the conversion and functional specialization of Treg into Tfr cells. (Source: Immunity)
Source: Immunity - December 12, 2017 Category: Allergy & Immunology Authors: Katharina Essig, Desheng Hu, Joao C. Guimaraes, Dominik Alterauge, Stephanie Edelmann, Timsse Raj, Jan Kranich, Gesine Behrens, Alexander Heiseke, Stefan Floess, Juliane Klein, Andreas Maiser, Susan Marschall, Martin Hrab ĕ de Angelis, Heinrich Leonhardt Tags: Article Source Type: research

Cystic Fibrosis Transmembrane Conductance Regulator Attaches Tumor Suppressor PTEN to the Membrane and Promotes Anti Pseudomonas aeruginosa Immunity
Anti-inflammatory PI3K-Akt signaling is suppressed in patients with cystic fibrosis (CF), a disease characterized by hyper-inflammatory responses to airway infection. Riquelme et  al. find that CFTR channel directly interacts with tumor suppressor PTEN, which regulates PI3K activity. CFTR helps position PTEN at the membrane to promote PTEN function and host immunity against Pseudomonas aeruginosa infection. (Source: Immunity)
Source: Immunity - December 12, 2017 Category: Allergy & Immunology Authors: Sebasti án A. Riquelme, Benjamin D. Hopkins, Andrew L. Wolfe, Emily DiMango, Kipyegon Kitur, Ramon Parsons, Alice Prince Tags: Article Source Type: research

Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA
Coelho et  al. demonstrate a post-transcriptional mechanism whereby oncogenic RAS signaling increases PD-L1 expression. Mechanistically, PD-L1 mRNA is targeted by TTP through AU-rich elements in the 3′ UTR, making it unstable. Oncogenic RAS signaling reduces TTP activity and stabilizes the PD-L1 transcript . Restoring TTP activity reduces PD-L1 expression and enhances anti-tumor immunity. (Source: Immunity)
Source: Immunity - December 12, 2017 Category: Allergy & Immunology Authors: Matthew A. Coelho, Sophie de Carn é Trécesson, Sareena Rana, Davide Zecchin, Christopher Moore, Miriam Molina-Arcas, Philip East, Bradley Spencer-Dene, Emma Nye, Karin Barnouin, Ambrosius P. Snijders, Wi S. Lai, Perry J. Blackshear, Julian Downward Tags: Article Source Type: research

Transcription Factor IRF4 Promotes CD8+ T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection
During chronic stimulation, CD8+ T  cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, loss of effector function, and metabolic impairments. Man et al. have identified a transcriptional module consisting of the TCR-induced transcription factors IRF4, BATF, and NFATc1 that drives T cell exhaus tion and impairs memory T cell development. (Source: Immunity)
Source: Immunity - December 12, 2017 Category: Allergy & Immunology Authors: Kevin Man, Sarah S. Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C. Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A. Febbraio, Wei Shi, Axel Kallies Tags: Article Source Type: research

High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization
Dendritic cells (DCs) are potent initiators of immune responses; however, human DC subsets have yet to be successfully harnessed for immunotherapies. By combining CyTOF and unbiased analysis, Alc ántara-Hernández et al. profile the heterogeneity of human DC subsets among individuals and tissues, providing comprehensive insights for the development of DC-based therapeutics. (Source: Immunity)
Source: Immunity - December 5, 2017 Category: Allergy & Immunology Authors: Marcela Alc ántara-Hernández, Rebecca Leylek, Lisa E. Wagar, Edgar G. Engleman, Tibor Keler, M. Peter Marinkovich, Mark M. Davis, Garry P. Nolan, Juliana Idoyaga Tags: Resource Source Type: research

Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction
CD4+ T  cells drive allogeneic organ transplant destruction, but how this is regulated transcriptionally remains unclear. Wu et al. report that IRF4 deletion in T cells leads to the establishment of T cell dysfunction and long-term allograft survival. Therefore, targeting IRF4 represents a therapeutic opportunity for achieving transplant acceptance. (Source: Immunity)
Source: Immunity - December 5, 2017 Category: Allergy & Immunology Authors: Jie Wu, Hedong Zhang, Xiaomin Shi, Xiang Xiao, Yihui Fan, Laurie J. Minze, Jin Wang, Rafik M. Ghobrial, Jiahong Xia, Roger Sciammas, Xian C. Li, Wenhao Chen Tags: Article Source Type: research

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection
The role of adipose tissue in protective immunity is largely unknown. Han et  al. reveal that white adipose tissue is a reservoir for memory T cells endowed with a distinct functional and metabolic profile. These memory T cells are able to protect against infection while inducing physiological remodeling of adipose tissue. (Source: Immunity)
Source: Immunity - December 5, 2017 Category: Allergy & Immunology Authors: Seong-Ji Han, Arielle Glatman Zaretsky, Vinicius Andrade-Oliveira, Nicholas Collins, Amiran Dzutsev, Jahangheer Shaik, Denise Morais da Fonseca, Oliver J. Harrison, Samira Tamoutounour, Allyson L. Byrd, Margery Smelkinson, Nicolas Bouladoux, James B. Blis Tags: Article Source Type: research

Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies
CSP is the target of protective antibodies against the malaria parasite Plasmodium falciparum (Pf). Here, Triller and Scally et  al. identified potent Pf-inhibitory human anti-CSP memory B cell antibodies induced by natural exposure and unveiled the molecular details of antigen binding to two protective CSP repeat epitopes. (Source: Immunity)
Source: Immunity - November 28, 2017 Category: Allergy & Immunology Authors: Gianna Triller, Stephen W. Scally, Giulia Costa, Maria Pissarev, Cornelia Kreschel, Alexandre Bosch, Eric Marois, Brandon K. Sack, Rajagopal Murugan, Ahmed M. Salman, Chris J. Janse, Shahid M. Khan, Stefan H.I. Kappe, Ayola A. Adegnika, Benjamin Mordm ül Tags: Article Source Type: research

The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages
Inflammasomes elicit pyroptosis or cell hyperactivation, with the latter defined as living cells that release IL-1. Evavold et  al report that the pore-forming protein gasdermin D regulates IL-1 release from hyperactive macrophages. Cell- and liposome-based assays revealed that gasdermin D pores permit IL-1 passage across intact lipid bilayers. (Source: Immunity)
Source: Immunity - November 28, 2017 Category: Allergy & Immunology Authors: Charles L. Evavold, Jianbin Ruan, Yunhao Tan, Shiyu Xia, Hao Wu, Jonathan C. Kagan Tags: Report Source Type: research

Tissue-Resident Macrophages Are Locally Programmed for Silent Clearance of Apoptotic Cells
Inappropriate inflammatory responses to apoptotic cells (ACs) can trigger autoimmune disease. Roberts et  al. now show that the tissue microenvironment programs resident macrophages so that clearance of ACs is linked to limited responses to AC-derived nucleic acids. This program is reversible upon removal of the macrophages from tissue and is dependent on the transcription factors KLF2 and KLF4. (Source: Immunity)
Source: Immunity - November 14, 2017 Category: Allergy & Immunology Authors: Allison W. Roberts, Bettina L. Lee, Jacques Deguine, Shinu John, Mark J. Shlomchik, Gregory M. Barton Tags: Article Source Type: research

A T Cell Receptor Locus Harbors a Malaria-Specific Immune Response Gene
CD8+ T  cells that recognize MHC I-peptide complexes contribute to protection or pathogenesis after infection. Van Braeckel-Budimir et al. demonstrate that a germline-encoded component of the T cell receptor functions as an Immune response (Ir) gene, controlling the CD8+ T cell response against a malar ia epitope and the outcome of infection. (Source: Immunity)
Source: Immunity - November 14, 2017 Category: Allergy & Immunology Authors: Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M. Josephs, Lecia Pewe, Stina L. Urban, Kelly L. Miners, Carine Farenc, David A. Price, Jamie Rossjohn, John T. Harty Tags: Article Source Type: research

Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity
T cell-APC interactions modulate outcomes in chronic viral infections, but the division of labor between APC subtypes is unclear. Chang et  al. reveal a dichotomy in costimulatory molecule expression whereby CD80 and CD86 are expressed mainly on classical DCs, and monocyte-derived APCs provide TNF family ligands for the post-priming accumulation of CD4+ T cells. (Source: Immunity)
Source: Immunity - November 14, 2017 Category: Allergy & Immunology Authors: Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L. Clouthier, Anh T. Tran, Miguel S. Torres Perez, Angela C. Zhou, Ali A. Abdul-Sater, Tania H. Watts Tags: Article Source Type: research

Targeting Interleukin-1 β Protects from Aortic Aneurysms Induced by Disrupted Transforming Growth Factor β Signaling
TGF- β signaling has an unquestionable but still controversial role in the pathogenesis of aortic aneurysm. Da Ros et al. demonstrate that disruption of TGF-β signaling in SMCs activates an autocrine IL-1β pathway that acts as a danger signal to recruit innate immune cells in the adventitia through C CL2. (Source: Immunity)
Source: Immunity - November 14, 2017 Category: Allergy & Immunology Authors: Francesco Da Ros, Raimondo Carnevale, Giuseppe Cifelli, Dario Bizzotto, Manuel Casaburo, Marialuisa Perrotta, Lorenzo Carnevale, Iolanda Vinciguerra, Stefania Fardella, Roberta Iacobucci, Giorgio M. Bressan, Paola Braghetta, Giuseppe Lembo, Daniela Carnev Tags: Article Source Type: research

The Cytokine TGF- β Promotes the Development and Homeostasis of Alveolar Macrophages
Alveolar macrophage (AM) development depends on GM-CSF, but whether additional factors regulate AMs is unknown. Yu et  al. identified TGF-β as another cytokine critical for the development and maturation of AMs. TGF-β regulated AMs in an autocrine manner and was also essential for their self-maintenance in adult mice. (Source: Immunity)
Source: Immunity - November 7, 2017 Category: Allergy & Immunology Authors: Xueyang Yu, Anne Buttgereit, Iva Lelios, Sebastian G. Utz, Dilay Cansever, Burkhard Becher, Melanie Greter Tags: Article Source Type: research

CD4+ T Cell Help Confers a Cytotoxic T Cell Effector Program Including Coinhibitory Receptor Downregulation and Increased Tissue Invasiveness
Cytotoxic T lymphocytes (CTLs) are important to eliminate virus-infected cells and cancer cells from the body. Ahrends et  al. reveal that CD4+ T cells help CTLs acquire their ability to perform this task through a specific gene program that involves the downregulation of coinhibitory receptors and increased motility and migration capacities. (Source: Immunity)
Source: Immunity - November 7, 2017 Category: Allergy & Immunology Authors: Tomasz Ahrends, Aldo Spanjaard, Bas Pilzecker, Nikolina B ąbała, Astrid Bovens, Yanling Xiao, Heinz Jacobs, Jannie Borst Tags: Article Source Type: research

Differentiation and Protective Capacity of Virus-Specific CD8 T Cells Suggest Murine Norovirus Persistence in an Immune-Privileged Enteric Niche
Chronic infections often cause T  cell dysfunction, but how noroviruses (NV) evade immunity is unknown. Tomov et al. show that gut-resident T cells against NV remain functional but ignorant of chronic viral replication, suggesting that NV persists in an immune-privileged enteric niche. (Source: Immunity)
Source: Immunity - October 11, 2017 Category: Allergy & Immunology Authors: Vesselin T. Tomov, Olesya Palko, Chi Wai Lau, Ajinkya Pattekar, Yuhang Sun, Ralitza Tacheva, Bertram Bengsch, Sasikanth Manne, Gabriela L. Cosma, Laurence C. Eisenlohr, Timothy J. Nice, Herbert W. Virgin, E. John Wherry Tags: Article Source Type: research

Store-Operated Ca Entry Controls Clonal Expansion of T Cells through Metabolic Reprogramming
Clonal expansion of T  cells is critical for protective immunity. Vaeth et al. (2017) demonstrate that store-operated calcium entry (SOCE), calcineurin, and NFAT control cell-cycle entry and proliferation of activated T cells through upregulation of glycolysis and oxidative phosphorylation. (Source: Immunity)
Source: Immunity - October 10, 2017 Category: Allergy & Immunology Authors: Martin Vaeth, Mate Maus, Stefan Klein-Hessling, Elizaveta Freinkman, Jun Yang, Miriam Eckstein, Scott Cameron, Stuart E. Turvey, Edgar Serfling, Friederike Berberich-Siebelt, Richard Possemato, Stefan Feske Tags: Article Source Type: research

Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation
Rapid neutrophil differentiation is key to the immune response against invading bacteria. Here, Riffelmacher et  al. show that autophagy, the main recycling process in the cell, provides energy for neutrophil differentiation by degrading lipid droplets. This opens possible novel therapeutic avenues for the differentiation treatment of granulocytic leukemia. (Source: Immunity)
Source: Immunity - September 12, 2017 Category: Allergy & Immunology Authors: Thomas Riffelmacher, Alexander Clarke, Felix C. Richter, Amanda Stranks, Sumeet Pandey, Sara Danielli, Philip Hublitz, Zhanru Yu, Errin Johnson, Tobias Schwerd, James McCullagh, Holm Uhlig, Sten Eirik W. Jacobsen, Anna Katharina Simon Tags: Article Source Type: research

Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development
Understanding the molecular basis for the development of HIV Env-specific bnAbs is key for vaccine design. Andrabi et  al. find that CAP256 V2 apex lineage Abs affinity mature with sialic acid containing complex-type glycans on HIV envelope trimer. This glycan recognition enables the development into bnAbs by resisting virus escape. (Source: Immunity)
Source: Immunity - September 12, 2017 Category: Allergy & Immunology Authors: Raiees Andrabi, Ching-Yao Su, Chi-Hui Liang, Sachin S. Shivatare, Bryan Briney, James E. Voss, Salar Khan Nawazi, Chung-Yi Wu, Chi-Huey Wong, Dennis R. Burton Tags: Article Source Type: research

SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition
Extracellular double-stranded RNA is predominantly sensed by cytosolic RLRs after endocytic uptake, but how it enters the cytoplasm is unknown. Nguyen and colleagues demonstrate that the endo-lysosomal protein SIDT2 transports double-stranded RNA into the cytoplasm for RLR signaling and is required for survival after EMCV infection. (Source: Immunity)
Source: Immunity - September 12, 2017 Category: Allergy & Immunology Authors: Tan A. Nguyen, Blake R.C. Smith, Michelle D. Tate, Gabrielle T. Belz, Marilou H. Barrios, Kirstin D. Elgass, Alexandra S. Weisman, Paul J. Baker, Simon P. Preston, Lachlan Whitehead, Alexandra Garnham, Rachel J. Lundie, Gordon K. Smyth, Marc Pellegrini, M Tags: Article Source Type: research

An NF- κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function
NF- κB regulates genes essential for conventional T cell activation and function, but its role in Treg cell function remains unclear. Oh et al. use Treg cell-specific conditional deletions of canonical NF-κB subunits to demonstrate central roles for p65 and c-Rel in orchestrating Treg cell developme nt, suppressive function, and molecular identity. (Source: Immunity)
Source: Immunity - September 7, 2017 Category: Allergy & Immunology Authors: Hyunju Oh, Yenkel Grinberg-Bleyer, Will Liao, Dillon Maloney, Pingzhang Wang, Zikai Wu, Jiguang Wang, Dev M. Bhatt, Nicole Heise, Roland M. Schmid, Matthew S. Hayden, Ulf Klein, Raul Rabadan, Sankar Ghosh Tags: Article Source Type: research

Phenolic Glycolipid Facilitates Mycobacterial Escape from Microbicidal Tissue-Resident Macrophages
Cambier et  al. find that activation of the STING pathway in lung-resident microbicidal macrophages by the mycobacterial surface lipid PGL enables bacterial escape by inducing the recruitment of mycobacterium-permissive monocytes via the CCL2-CCR2 chemokine axis. Their findings reveal a relocation strategy th at enables mycobacterial dissemination, and argue for the potential of interventions targeting PGL in the prevention of tuberculosis. (Source: Immunity)
Source: Immunity - August 24, 2017 Category: Allergy & Immunology Authors: C.J. Cambier, Se ónadh M. O’Leary, Mary P. O’Sullivan, Joseph Keane, Lalita Ramakrishnan Tags: Article Source Type: research

Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition
Inflammasomes were proposed to shape gut ecology based on dysbiosis in mutant mice versus non-littermate wild-types. Mamantopoulos et  al. show that inflammasomes do not affect gut microbiota composition when controlling for non-genetic confounders. This finding dismisses the suggested role for inflammasomes in controlling host health through regulation of intestinal ecology. (Source: Immunity)
Source: Immunity - August 8, 2017 Category: Allergy & Immunology Authors: Michail Mamantopoulos, Francesca Ronchi, Filip Van Hauwermeiren, Sara Vieira-Silva, Bahtiyar Yilmaz, Liesbet Martens, Yvan Saeys, Stefan K. Drexler, Amir S. Yazdi, Jeroen Raes, Mohamed Lamkanfi, Kathy D. McCoy, Andy Wullaert Tags: Article Source Type: research

Anti-Inflammatory Chromatinscape Suggests Alternative Mechanisms of Glucocorticoid Receptor Action
Although glucocorticoids are widely used anti-inflammatory drugs, relevant mechanisms are unclear. Oh et  al. monitored the epigenomic landscape of macrophages and found that the gene-inducing activity of GR is crucial for boosting inhibitors of inflammatory factors. This cautions the idea that GR ligands selectively promoting trans-repression should improve therapeutic outcome. (Source: Immunity)
Source: Immunity - August 8, 2017 Category: Allergy & Immunology Authors: Kyu-Seon Oh, Heta Patel, Rachel A. Gottschalk, Wai Shing Lee, Songjoon Baek, Iain D.C. Fraser, Gordon L. Hager, Myong-Hee Sung Tags: Article Source Type: research

Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein α Signaling
It is unclear how DNA sensing by DCs is superior to macrophages. Xu et  al. show that DCs are specialized in sensing mtDNA after CD47 blockade through inhibiting uptaken DNA degradation in their phagosomes while macrophages rapidly degrade DNA. (Source: Immunity)
Source: Immunity - August 8, 2017 Category: Allergy & Immunology Authors: Meng Michelle Xu, Yang Pu, Dali Han, Yaoyao Shi, Xuezhi Cao, Hua Liang, Xiang Chen, Xiao-Dong Li, Liufu Deng, Zhijian J. Chen, Ralph R. Weichselbaum, Yang-Xin Fu Tags: Article Source Type: research

T Cell Zone Resident Macrophages Silently Dispose of Apoptotic Cells in the Lymph Node
Dendritic cells (DCs) in the lymph node (LN) T  cell zone are thought to be central to the clearance of apoptotic cells and T cell priming. Baratin et al. identify a population of LN macrophages that act as the sole professional scavengers in this area, suggesting that silent efferocytosis and T cell activation in the LN paracortex involve t wo different cell types—macrophages and DCs, respectively. (Source: Immunity)
Source: Immunity - August 8, 2017 Category: Allergy & Immunology Authors: Myriam Baratin, L éa Simon, Audrey Jorquera, Clément Ghigo, Doulaye Dembele, Jonathan Nowak, Rebecca Gentek, Stephan Wienert, Frederick Klauschen, Bernard Malissen, Marc Dalod, Marc Bajénoff Tags: Article Source Type: research