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Journal of Immunology: Official Journal of the American Association of Immunologists

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https://www.readbyqxmd.com/read/30232138/the-histone-demethylase-lsd1-regulates-b-cell-proliferation-and-plasmablast-differentiation
#1
Robert R Haines, Benjamin G Barwick, Christopher D Scharer, Parimal Majumder, Troy D Randall, Jeremy M Boss
B cells undergo epigenetic remodeling as they differentiate into Ab-secreting cells (ASC). LSD1 is a histone demethylase known to decommission active enhancers and cooperate with the ASC master regulatory transcription factor Blimp-1. The contribution of LSD1 to ASC formation is poorly understood. In this study, we show that LSD1 is necessary for proliferation and differentiation of mouse naive B cells (nB) into plasmablasts (PB). Following LPS inoculation, LSD1-deficient hosts exhibited a 2-fold reduction of splenic PB and serum IgM...
September 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30232137/diversification-of-bw4-specificity-and-recognition-of-a-nonclassical-mhc-class-i-molecule-implicated-in-maternal-fetal-tolerance-by-killer-cell-ig-like-receptors-of-the-rhesus-macaque
#2
Priyankana Banerjee, Moritz Ries, Sanath Kumar Janaka, Andres G Grandea, Roger Wiseman, David H O'Connor, Thaddeus G Golos, David T Evans
The rhesus macaque is an important animal model for AIDS and other infectious diseases; however, studies to address NK cell function in this species have been limited by the lack of defined ligands for killer cell Ig-like receptors (KIRs). To identify ligands for rhesus macaque KIRs, we adopted a novel approach based on a pair of stable cell lines. NFAT-responsive luciferase reporter cell lines expressing the extracellular domains of macaque KIRs fused to the transmembrane and cytoplasmic domains of CD28 and CD3ζ were incubated with target cells expressing individual MHC class I molecules, and ligand recognition was detected by the MHC class I-dependent upregulation of luciferase...
September 19, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30224514/il-17a-attenuates-ifn-%C3%AE-expression-by-inducing-suppressor-of-cytokine-signaling-expression-in-airway-epithelium
#3
Mitsuru Niwa, Tomoyuki Fujisawa, Kazutaka Mori, Katsumasa Yamanaka, Hideki Yasui, Yuzo Suzuki, Masato Karayama, Hironao Hozumi, Kazuki Furuhashi, Noriyuki Enomoto, Yutaro Nakamura, Naoki Inui, Tetsuro Suzuki, Masato Maekawa, Takafumi Suda
IFN-λ is a cytokine expressed in epithelial tissues and plays a central role in antiviral mucosal immune response. The expression of IFN-λ in the airway is impaired in chronic airway diseases (e.g., asthma, chronic obstructive pulmonary disease), which renders patients susceptible to viral infection. IL-17A is associated with asthma and chronic obstructive pulmonary disease pathogenesis; however, IL-17A regulation of IFN-λ expression remains unclear. The aim of the current study is to clarify IL-17A-mediated regulatory mechanisms of IFN-λ expression in human airway epithelial cells...
September 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30224513/d-glycero-%C3%AE-d-manno-heptose-1-phosphate-and-d-glycero-%C3%AE-d-manno-heptose-1-7-biphosphate-are-both-innate-immune-agonists
#4
Itunuoluwa A Adekoya, Cynthia X Guo, Scott D Gray-Owen, Andrew D Cox, Janelle Sauvageau
d-Glycero-β-d-manno-heptose 1,7-biphosphate (β-HBP) is a novel microbial-associated molecular pattern that triggers inflammation and thus has the potential to act as an immune modulator in many therapeutic contexts. To better understand the structure-activity relationship of this molecule, we chemically synthesized analogs of β-HBP and tested their ability to induce canonical TIFA-dependent inflammation in human embryonic kidney cells (HEK 293T) and colonic epithelial cells (HCT 116). Of the analogs tested, only d-glycero-β-d-manno-heptose 1-phosphate (β-HMP) induced TIFA-dependent NF-κB activation and cytokine production in a manner similar to β-HBP...
September 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30224512/therapeutic-potential-of-mesenchymal-cell-derived-mirna-150-5p-expressing-exosomes-in-rheumatoid-arthritis-mediated-by-the-modulation-of-mmp14-and-vegf
#5
Zhe Chen, Hanqi Wang, Yang Xia, Fuhua Yan, Yong Lu
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial tissue inflammation and joint destruction associated with the activation of angiogenesis. Exosomes, which play a role in cell-to-cell communication as carriers of genetic information, transfer microRNAs (miRNAs or miRs) between cells and have been studied as delivery vehicles for therapeutic molecules. The aim of the current study was to investigate the therapeutic effect of mesenchymal stem cell (MSC)-derived miR-150-5p exosomes on joint destruction in RA...
September 17, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30217830/neutrophil-vaccination-dynamics-and-their-capacity-to-mediate-b-cell-help-in-rhesus-macaques
#6
Thomas Musich, Mohammad Arif Rahman, Venkatramanan Mohanram, Leia Miller-Novak, Thorsten Demberg, David J Venzon, Barbara K Felber, Genoveffa Franchini, George N Pavlakis, Marjorie Robert-Guroff
Neutrophils are the most abundant leukocyte and play a critical role in the initial response to an Ag. Recently, their ability to contribute to adaptive immunity has been highlighted. We evaluated the ability of neutrophils from blood to contribute to the adaptive immune response in a preclinical rhesus macaque SIV vaccine trial. Replication-competent adenovirus-SIV recombinants induced neutrophil activation, B cell help markers, and enhanced ability to generate reactive oxygen species. Boosting with SIV vaccines (adjuvant together with ALVAC or DNA plus envelope protein) elicited significant neutrophil responses...
September 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30217829/observed-antibody-space-a-resource-for-data-mining-next-generation-sequencing-of-antibody-repertoires
#7
Aleksandr Kovaltsuk, Jinwoo Leem, Sebastian Kelm, James Snowden, Charlotte M Deane, Konrad Krawczyk
Abs are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made Abs the primary class of biopharmaceuticals. Recently, it has become possible to query their immense natural diversity using next-generation sequencing of Ig gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis...
September 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30217828/correction-cross-presentation-of-soluble-and-cell-associated-antigen-by-murine-hepatocytes-is-enhanced-by-collectrin-expression
#8
Joseph S Dolina, Sylvia Cechova, Christine K Rudy, Sun-Sang J Sung, William W Tang, Joey Lee, Young S Hahn, Thu H Le
No abstract text is available yet for this article.
September 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209193/cardiotrophin-like-cytokine-increases-macrophage-foam-cell-transition
#9
Sarah Pasquin, Véronique Laplante, Shiriane Kouadri, Andreea Milasan, Gaétan Mayer, Aurélie Jeanne Tormo, Virginia Savin, Mukut Sharma, Catherine Martel, Jean-François Gauchat
CLCF1 is a neurotrophic and B cell-stimulating factor belonging to the IL-6 family. Mutations in the gene coding for CLCF1 or its secretion partner CRLF1 lead to the development of severe phenotypes, suggesting important nonredundant roles in development, metabolism, and immunity. Although CLCF1 was shown to promote the proliferation of the myeloid cell line M1, its roles on myeloid activation remain underinvestigated. We characterized the effects of CLCF1 on myeloid cells with a focus on monocyte-macrophage and macrophage-foam cell differentiations...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209192/chemotherapy-combines-effectively-with-anti-pd-l1-treatment-and-can-augment-antitumor-responses
#10
Rafael Cubas, Marina Moskalenko, Jeanne Cheung, Michelle Yang, Erin McNamara, Huizhong Xiong, Sabine Hoves, Carola H Ries, Jeong Kim, Stephen Gould
Immunotherapy with checkpoint inhibitors has proved to be highly effective, with durable responses in a subset of patients. Given their encouraging clinical activity, checkpoint inhibitors are increasingly being tested in clinical trials in combination with chemotherapy. In many instances, there is little understanding of how chemotherapy might influence the quality of the immune response generated by checkpoint inhibitors. In this study, we evaluated the impact of chemotherapy alone or in combination with anti-PD-L1 in a responsive syngeneic tumor model...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209191/cutting-edge-the-heat-shock-protein-gp96-activates-inflammasome-signaling-platforms-in-apcs
#11
Yifei Wang, Abigail L Sedlacek, Sudesh Pawaria, Haiyan Xu, Melanie J Scott, Robert J Binder
Several heat shock proteins (HSPs) prime immune responses, which are, in part, a result of activation of APCs. APCs respond to these immunogenic HSPs by upregulating costimulatory molecules and secreting cytokines, including IL-1β. These HSP-mediated responses are central mediators in pathological conditions ranging from cancer, sterile inflammation associated with trauma, and rheumatoid arthritis. We tested in this study the requirement of inflammasomes in the release of IL-1β by one immunogenic HSP, gp96...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209190/cutting-edge-tgf-%C3%AE-and-phosphatidylinositol-3-kinase-signals-modulate-distinct-metabolism-of-regulatory-t-cell-subsets
#12
Bhavana Priyadharshini, Michael Loschi, Ryan H Newton, Jian-Wen Zhang, Kelsey K Finn, Valerie A Gerriets, Alexandria Huynh, Jeffery C Rathmell, Bruce R Blazar, Laurence A Turka
Murine Foxp3+ regulatory T cells (Tregs) differentiated in vitro (induced Tregs [iTregs]) in the presence of anti-inflammatory cytokine TGF-β rely predominantly upon lipid oxidation to fuel mitochondrial oxidative phosphorylation. Foxp3 expression underlies this metabolic preference, as it suppresses glycolysis and drives oxidative phosphorylation. In this study, we show that in contrast to iTregs, thymic-derived Tregs (tTregs), engage in glycolysis and glutaminolysis at levels comparable to effector T cells despite maintained Foxp3 expression...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209189/influenza-a-virus-infection-causes-chronic-lung-disease-linked-to-sites-of-active-viral-rna-remnants
#13
Shamus P Keeler, Eugene V Agapov, Michael E Hinojosa, Adam N Letvin, Kangyun Wu, Michael J Holtzman
Clinical and experimental observations suggest that chronic lung disease is linked to respiratory viral infection. However, the long-term aspect of this relationship is not yet defined using a virus that replicates at properly high levels in humans and a corresponding animal model. In this study, we show that influenza A virus infection achieves 1 × 106 -fold increases in viral load in the lung and dose-dependent severity of acute illness in mice. Moreover, these events are followed by persistence of negative- and positive-strand viral RNA remnants for 15 wk and chronic lung disease for at least 26 wk postinfection...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209188/bmi1-regulates-i%C3%AE%C2%BAb%C3%AE-degradation-via-association-with-the-scf-complex
#14
Yuko Okuyama, Yuki Tanaka, Jing-Jing Jiang, Daisuke Kamimura, Akihiro Nakamura, Mitsutoshi Ota, Takuto Ohki, Daisuke Higo, Hideki Ogura, Naoto Ishii, Toru Atsumi, Masaaki Murakami
Bmi1 is a polycomb group protein and regulator that stabilizes the ubiquitination complex PRC1 in the nucleus with no evidently direct link to the NF-κB pathway. In this study, we report a novel function of Bmi1: its regulation of IκBα ubiquitination in the cytoplasm. A deficiency of Bmi1 inhibited NF-κB-mediated gene expression in vitro and a NF-κB-mediated mouse model of arthritis in vivo. Mechanistic analysis showed that Bmi1 associated with the SCF ubiquitination complex via its N terminus and with phosphorylation by an IKKα/β-dependent pathway, leading to the ubiquitination of IκBα...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30209187/baculovirus-induced-fast-acting-innate-immunity-kills-liver-stage-plasmodium
#15
Talha Bin Emran, Mitsuhiro Iyori, Yuki Ono, Fitri Amelia, Yenni Yusuf, Ashekul Islam, Asrar Alam, Megumi Tamura, Ryohei Ogawa, Hiroyuki Matsuoka, Daisuke S Yamamoto, Shigeto Yoshida
Baculovirus (BV), an enveloped insect virus with a circular dsDNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. In this study, we show that BV administration in BALB/c mice not only provides complete protection against a subsequent Plasmodium berghei sporozoite infection for up to 7 d after the injection but also eliminates existing liver-stage parasites completely. The elimination of sporozoites by BV was superior to that by primaquine, and this effect occurred in a TLR9-independent manner...
September 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30201812/presenilin-1-regulates-nf-%C3%AE%C2%BAb-activation-via-association-with-breakpoint-cluster-region-and-casein-kinase-ii
#16
Yuki Tanaka, Lavannya Sabharwal, Mitsutoshi Ota, Ikuma Nakagawa, Jing-Jing Jiang, Yasunobu Arima, Hideki Ogura, Masayasu Okochi, Masaru Ishii, Daisuke Kamimura, Masaaki Murakami
We recently reported that NF-κB-mediated inflammation caused by breakpoint cluster region (BCR) is dependent on the α subunit of casein kinase II (CK2α) complex. In the current study, we demonstrate that presenilin 1 (Psen1), which is a catalytic component of the γ-secretase complex and the mutations of which are known to cause familial Alzheimer disease, acts as a scaffold of the BCR-CK2α-p65 complex to induce NF-κB activation. Indeed, Psen1 deficiency in mouse endothelial cells showed a significant reduction of NF-κB p65 recruitment to target gene promoters...
September 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30201811/%C3%AE-1-integrins-are-required-to-mediate-nk-cell-killing-of-cryptococcus-neoformans
#17
Richard F Xiang, ShuShun Li, Henry Ogbomo, Danuta Stack, Christopher H Mody
Cryptococcus neoformans is a fungal pathogen that causes fatal meningitis and pneumonia. During host defense to Cryptococcus , NK cells directly recognize and kill C. neoformans using cytolytic degranulation analogous to killing of tumor cells. This fungal killing requires independent activation of Src family kinase (SFK) and Rac1-mediated pathways. Recognition of C. neoformans requires the natural cytotoxicity receptor, NKp30; however, it is not known whether NKp30 activates both signal transduction pathways or whether a second receptor is involved in activation of one of the pathways...
September 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30201810/oxidant-signaling-mediated-by-nox2-in-neutrophils-promotes-regenerative-myelopoiesis-and-tissue-recovery-following-ischemic-damage
#18
Milie M Fang, Pijus K Barman, Muthusamy Thiruppathi, Rita E Mirza, Ronald D McKinney, Jing Deng, John W Christman, Xiaoping Du, Tohru Fukai, William J Ennis, Timothy J Koh, Masuko Ushio-Fukai, Norifumi Urao
Ischemic tissue damage activates hematopoietic stem and progenitor cells (HSPCs) in the bone marrow (BM)-generating myeloid cells, and persistent HSPC activity may drive chronic inflammation and impair tissue recovery. Although increased reactive oxygen species in the BM regulate HSPC functions, their roles in myelopoiesis of activated HSPCs and subsequent tissue recovery during ischemic damage are not well understood. In this paper, we report that deletion of Nox2 NADPH oxidase in mice results in persistent elevations in BM HSPC activity and levels of inflammatory monocytes/macrophages in BM and ischemic tissue in a model of hindlimb ischemia...
September 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30201809/cutting-edge-intracellular-ifn-%C3%AE-and-distinct-type-i-ifn-expression-patterns-in-circulating-systemic-lupus-erythematosus-b-cells
#19
Jennie A Hamilton, Qi Wu, PingAr Yang, Bao Luo, Shanrun Liu, Jun Li, Alexa L Mattheyses, Ignacio Sanz, W Winn Chatham, Hui-Chen Hsu, John D Mountz
In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I IFN-stimulated genes (ISG) and can drive B cells to produce autoantibodies. Little is known about the expression of distinct type I IFNs in lupus, particularly high-affinity IFN-β. Single-cell analyses of transitional B cells isolated from SLE patients revealed distinct B cell subpopulations, including type I IFN producers, IFN responders, and mixed IFN producer/responder clusters. Anti-Ig plus TLR3 stimulation of SLE B cells induced release of bioactive type I IFNs that could stimulate HEK-Blue cells...
September 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30201808/phenotypic-and-functional-signatures-of-herpes-simplex-virus-specific-effector-memory-cd73-cd45ra-high-ccr7-low-cd8-t-emra-and-cd73-cd45ra-low-ccr7-low-cd8-t-em-cells-are-associated-with-asymptomatic-ocular-herpes
#20
Ruchi Srivastava, Pierre-Grégoire Coulon, Soumyabrata Roy, Sravya Chilukuri, Sumit Garg, Lbachir BenMohamed
HSV type 1 (HSV-1)-specific CD8+ T cells protect from herpes infection and disease. However, the nature of protective CD8+ T cells in HSV-1 seropositive healthy asymptomatic (ASYMP) individuals (with no history of clinical herpes disease) remains to be determined. In this study, we compared the phenotype and function of HSV-specific CD8+ T cells from HLA-A*02:01-positive ASYMP and symptomatic (SYMP) individuals (with a documented history of numerous episodes of recurrent ocular herpetic disease). We report that although SYMP and ASYMP individuals have similar frequencies of HSV-specific CD8+ T cells, the "naturally" protected ASYMP individuals have a significantly higher proportion of multifunctional HSV-specific effector memory CD8+ T cells (CD73+ CD45RAhigh CCR7low CD8+ effector memory RA (TEMRA ) and CD73+ CD45RAlow CCR7low CD8+ effector memory (TEM ) as compared with SYMP individuals...
September 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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