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

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https://www.readbyqxmd.com/read/28724580/il-7-restores-t-lymphocyte-immunometabolic-failure-in-septic-shock-patients-through-mtor-activation
#1
Fabienne Venet, Julie Demaret, Benjamin J Blaise, Christelle Rouget, Thibaut Girardot, Estellie Idealisoa, Thomas Rimmelé, François Mallet, Alain Lepape, Julien Textoris, Guillaume Monneret
T lymphocyte alterations are central to sepsis pathophysiology, whereas related mechanisms remain poorly understood. We hypothesized that metabolic alterations could play a role in sepsis-induced T lymphocyte dysfunction. Samples from septic shock patients were obtained at day 3 and compared with those from healthy donors. T cell metabolic status was evaluated in the basal condition and after T cell stimulation. We observed that basal metabolic content measured in lymphocytes by nuclear magnetic resonance spectroscopy was altered in septic patients...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28724579/novel-bivalent-viral-vectored-vaccines-induce-potent-humoral-and-cellular-immune-responses-conferring-protection-against-stringent-influenza-a-virus-challenge
#2
Claire M Tully, Senthil Chinnakannan, Caitlin E Mullarkey, Marta Ulaszewska, Francesca Ferrara, Nigel Temperton, Sarah C Gilbert, Teresa Lambe
Seasonal influenza viruses are a common cause of acute respiratory illness worldwide and generate a significant socioeconomic burden. Influenza viruses mutate rapidly, necessitating annual vaccine reformulation because traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality compared with seasonal strains...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28724578/induction-of-regulatory-t-cells-and-its-regulation-with-insulin-like-growth-factor-insulin-like-growth-factor-binding-protein-4-by-human-mesenchymal-stem-cells
#3
Ippei Miyagawa, Shingo Nakayamada, Kazuhisa Nakano, Kaoru Yamagata, Kei Sakata, Kunihiro Yamaoka, Yoshiya Tanaka
Human mesenchymal stem cells (MSCs) are multipotent and exert anti-inflammatory effects, but the underlying mechanism remains to be elucidated. In the current study, we investigated the regulatory mechanism of regulatory T cell (Treg) induction through the growth factors released by human MSCs. Human naive CD4(+) T cells were stimulated with anti-CD3/28 Abs and cocultured with human MSC culture supernatant for 48 h. The proliferation and cytokine production of CD4(+) T cells and surface molecule expression on CD4(+) T cells were evaluated...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716827/galectin-1-driven-tolerogenic-programs-aggravate-yersinia-enterocolitica-infection-by-repressing-antibacterial-immunity
#4
Roberto C Davicino, Santiago P Méndez-Huergo, Ricardo J Eliçabe, Juan C Stupirski, Ingo Autenrieth, María S Di Genaro, Gabriel A Rabinovich
Yersinia enterocolitica is an enteropathogenic bacterium that causes gastrointestinal disorders, as well as extraintestinal manifestations. To subvert the host's immune response, Y. enterocolitica uses a type III secretion system consisting of an injectisome and effector proteins, called Yersinia outer proteins (Yops), that modulate activation, signaling, and survival of immune cells. In this article, we show that galectin-1 (Gal-1), an immunoregulatory lectin widely expressed in mucosal tissues, contributes to Y...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716826/il-10-producing-infliximab-specific-t-cells-regulate-the-antidrug-t-cell-response-in-exposed-patients
#5
Alessandra Vultaggio, Francesca Nencini, Sara Pratesi, Daniele Cammelli, Maria Totaro, Sergio Romagnani, Enrico Maggi, Andrea Matucci
Infliximab (IFX) is a chimeric mAb that can lead to the appearance of anti-drug Abs. Recent research has identified the presence of circulating IFX-specific T cells in treated patients. The aim of the study was to analyze the functional characteristics of IFX-specific T cells, in particular their capability to produce biologically active regulatory cytokines. Drug-stimulated PBMCs or coculture systems were used to detect memory T cells in treated patients. The cytokines produced by IFX-specific T cells, T cell lines, and T cell clones were evaluated at the mRNA and protein levels...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28716825/efficiency-and-safety-of-crac-inhibitors-in-human-rheumatoid-arthritis-xenograft-models
#6
Shuang Liu, Hitoshi Hasegawa, Erika Takemasa, Yasuyuki Suzuki, Keizou Oka, Takeshi Kiyoi, Hiroyuki Takeda, Tomio Ogasawara, Tatsuya Sawasaki, Masaki Yasukawa, Kazutaka Maeyama
Store-operated Ca(2+) release-activated Ca(2+) (CRAC) channels are involved in the pathogenesis of rheumatoid arthritis (RA) and have been studied as therapeutic targets in the management of RA. We investigated the efficacy and safety of CRAC inhibitors, including a neutralizing Ab (hCRACM1-IgG) and YM-58483, in the treatment of RA. Patient-derived T cell and B cell activity was suppressed by hCRACM1-IgG as well as YM-58483. Systemically constant, s.c. infused CRAC inhibitors showed anti-inflammatory activity in a human-NOD/SCID xenograft RA model as well as protective effects against the destruction of cartilage and bone...
July 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710255/cathelicidins-inhibit-escherichia-coli-induced-tlr2-and-tlr4-activation-in-a-viability-dependent-manner
#7
Maarten Coorens, Viktoria A F Schneider, A Marit de Groot, Albert van Dijk, Marjolein Meijerink, Jerry M Wells, Maaike R Scheenstra, Edwin J A Veldhuizen, Henk P Haagsman
Activation of the immune system needs to be tightly regulated to provide protection against infections and, at the same time, to prevent excessive inflammation to limit collateral damage to the host. This tight regulation includes regulating the activation of TLRs, which are key players in the recognition of invading microbes. A group of short cationic antimicrobial peptides, called cathelicidins, have previously been shown to modulate TLR activation by synthetic or purified TLR ligands and may play an important role in the regulation of inflammation during infections...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710254/the-plasticity-and-stability-of-regulatory-t-cells-during-viral-induced-inflammatory-lesions
#8
Siddheshvar Bhela, Siva Karthik Varanasi, Ujjaldeep Jaggi, Sarah S Sloan, Naveen K Rajasagi, Barry T Rouse
Ocular infection with HSV causes a chronic T cell-mediated inflammatory lesion in the cornea. Lesion severity is affected by the balance of different CD4 T cell subsets, with greater severity occurring when the activity of regulatory T cells (Tregs) is compromised. In this study, fate-mapping mice were used to assess the stability of Treg function in ocular lesions. We show that cells that were once Foxp3(+) functional Tregs may lose Foxp3 and become Th1 cells that could contribute to lesion expression. The instability primarily occurred with IL-2R(lo) Tregs and was shown, in part, to be the consequence of exposure to IL-12...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710253/dual-immunization-with-sseb-flagellin-provides-enhanced-protection-against-salmonella-infection-mediated-by-circulating-memory-cells
#9
Seung-Joo Lee, Joseph Benoun, Brian S Sheridan, Zachary Fogassy, Oanh Pham, Quynh-Mai Pham, Lynn Puddington, Stephen J McSorley
The development of a subunit Salmonella vaccine has been hindered by the absence of detailed information about antigenic targets of protective Salmonella-specific T and B cells. Recent studies have identified SseB as a modestly protective Ag in susceptible C57BL/6 mice, but the mechanism of protective immunity remains undefined. In this article, we report that simply combining Salmonella SseB with flagellin substantially enhances protective immunity, allowing immunized C57BL/6 mice to survive for up to 30 d following challenge with virulent bacteria...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710252/an-unbiased-linkage-approach-reveals-that-the-p53-pathway-is-coupled-to-nk-cell-maturation
#10
Roxanne Collin, Charles St-Pierre, Lorie Guilbault, Victor Mullins-Dansereau, Antonia Policheni, Fanny Guimont-Desrochers, Adam-Nicolas Pelletier, Daniel H Gray, Elliot Drobetsky, Claude Perreault, Erin E Hillhouse, Sylvie Lesage
Natural killer cells constitute potent innate lymphoid cells that play a major role in both tumor immunosurveillance and viral clearance via their effector functions. A four-stage model of NK cell functional maturation has been established according to the expression of CD11b and CD27, separating mature NK (mNK) cells into distinct populations that exhibit specific phenotypic and functional properties. To identify genetic factors involved in the regulation of NK cell functional maturation, we performed a linkage analysis on F2 (B6...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710251/role-for-zap-70-signaling-in-the-differential-effector-functions-of-rituximab-and-obinutuzumab-ga101-in-chronic-lymphocytic-leukemia-b-cells
#11
Sladjana Skopelja-Gardner, Jonathan D Jones, B JoNell Hamilton, Alexey V Danilov, William F C Rigby
Rituximab (RTX) has been the hallmark anti-CD20 mAb for the treatment of B cell neoplasms, including B cell chronic lymphocytic leukemia (B-CLL). Recently, a novel humanized anti-CD20 mAb obinutuzumab (GA101) has been implemented as first-line CLL therapy. Treatment of CLL patients with RTX is associated with CD20 loss via an FcγR-mediated process, trogocytosis. RTX-induced trogocytosis has been characterized as both the means of resistance to therapy, via loss of cell surface target proteins (antigenic modulation), as well as a process that alters B cell phenotype and function...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28710250/near-infrared-1064-nm-laser-modulates-migratory-dendritic-cells-to-augment-the-immune-response-to-intradermal-influenza-vaccine
#12
Kaitlyn Morse, Yoshifumi Kimizuka, Megan P K Chan, Mai Shibata, Yusuke Shimaoka, Shu Takeuchi, Benjamin Forbes, Christopher Nirschl, Binghao Li, Yang Zeng, Roderick T Bronson, Wataru Katagiri, Ayako Shigeta, Ruxandra F Sîrbulescu, Huabiao Chen, Rhea Y Y Tan, Kosuke Tsukada, Timothy Brauns, Jeffrey Gelfand, Ann Sluder, Joseph J Locascio, Mark C Poznansky, Niroshana Anandasabapathy, Satoshi Kashiwagi
Brief exposure of skin to near-infrared (NIR) laser light has been shown to augment the immune response to intradermal vaccination and thus act as an immunologic adjuvant. Although evidence indicates that the NIR laser adjuvant has the capacity to activate innate subsets including dendritic cells (DCs) in skin as conventional adjuvants do, the precise immunological mechanism by which the NIR laser adjuvant acts is largely unknown. In this study we sought to identify the cellular target of the NIR laser adjuvant by using an established mouse model of intradermal influenza vaccination and examining the alteration of responses resulting from genetic ablation of specific DC populations...
July 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#13
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701511/n-arachidonoyl-dopamine-modulates-acute-systemic-inflammation-via-nonhematopoietic-trpv1
#14
Samira K Lawton, Fengyun Xu, Alphonso Tran, Erika Wong, Arun Prakash, Mark Schumacher, Judith Hellman, Kevin Wilhelmsen
N-Arachidonoyl dopamine (NADA) is an endogenous lipid that potently activates the transient receptor potential vanilloid 1 (TRPV1), which mediates pain and thermosensation. NADA is also an agonist of cannabinoid receptors 1 and 2. We have reported that NADA reduces the activation of cultured human endothelial cells by LPS and TNF-α. Thus far, in vivo studies using NADA have focused on its neurologic and behavioral roles. In this article, we show that NADA potently decreases in vivo systemic inflammatory responses and levels of the coagulation intermediary plasminogen activator inhibitor 1 in three mouse models of inflammation: LPS, bacterial lipopeptide, and polymicrobial intra-abdominal sepsis...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701510/immunomodulatory-molecule-irak-m-balances-macrophage-polarization-and-determines-macrophage-responses-during-renal-fibrosis
#15
Stefanie Steiger, Santhosh V Kumar, Mohsen Honarpisheh, Georg Lorenz, Roman Günthner, Simone Romoli, Regina Gröbmayr, Heni-Eka Susanti, Jan Potempa, Joanna Koziel, Maciej Lech
Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD)...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701509/dendritic-cell-derived-il-32%C3%AE-a-novel-inhibitory-cytokine-of-nk-cell-function
#16
Laurent Gorvel, Daniel Korenfeld, Thomas Tung, Eynav Klechevsky
Cytokines produced by dendritic cells (DCs) can largely determine the direction of immunity. Transcriptional analysis revealed that besides IL-15, IL-32 was the only other cytokine expressed by human Langerhans cells. IL-32 is a human cytokine that exists in four main isoforms. Currently, little is known about the regulation and function of the various IL-32 isoforms. In this study, we found that IL-15 is a potent inducer of IL-32α in DCs. Because IL-15 promotes NK cell activation, we investigated the interplay between IL-32 and IL-15 and their role in NK cell activity...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701508/prdm1-regulates-thymic-epithelial-function-to-prevent-autoimmunity
#17
Natalie A Roberts, Brian D Adams, Nicholas I McCarthy, Reuben M Tooze, Sonia M Parnell, Graham Anderson, Susan M Kaech, Valerie Horsley
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28701507/the-innate-cytokines-il-25-il-33-and-tslp-cooperate-in-the-induction-of-type-2-innate-lymphoid-cell-expansion-and-mucous-metaplasia-in-rhinovirus-infected-immature-mice
#18
Mingyuan Han, Charu Rajput, Jun Y Hong, Jing Lei, Joanna L Hinde, Qian Wu, J Kelley Bentley, Marc B Hershenson
Early-life respiratory viral infection is a risk factor for asthma development. Rhinovirus (RV) infection of 6-d-old mice, but not mature mice, causes mucous metaplasia and airway hyperresponsiveness that are associated with the expansion of lung type 2 innate lymphoid cells (ILC2s) and are dependent on IL-13 and the innate cytokine IL-25. However, contributions of the other innate cytokines, IL-33 and thymic stromal lymphopoietin (TSLP), to the observed asthma-like phenotype have not been examined. We reasoned that IL-33 and TSLP expression are also induced by RV infection in immature mice and are required for maximum ILC2 expansion and mucous metaplasia...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28696256/a-novel-subset-of-anti-inflammatory-cd138-macrophages-is-deficient-in-mice-with-experimental-lupus
#19
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Hui Li, Li-Jun Yang, Westley H Reeves
Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4(+)) large peritoneal MΦ...
July 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28696255/regulated-polarization-of-tumor-associated-macrophages-by-mir-145-via-colorectal-cancer-derived-extracellular-vesicles
#20
Haruka Shinohara, Yuki Kuranaga, Minami Kumazaki, Nobuhiko Sugito, Yuki Yoshikawa, Tomoaki Takai, Kohei Taniguchi, Yuko Ito, Yukihiro Akao
Macrophages are polarized into functional classically activated and alternatively activated (M2) phenotypes depending on their microenvironment, and these cells play an important role in the immune system. M2-like polarization of tumor-associated macrophages (TAMs) is activated by various secretions from cancer cells; however, the interaction between cancer cells and TAMs is not well understood. Recent studies showed that cancer cell-derived extracellular vesicles (EVs) contribute to tumor development and modulation of the tumor microenvironment...
July 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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