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https://www.readbyqxmd.com/read/29166752/immunotherapy-treatment-an-issue-for-metabolic-response
#1
Luca Tagliabue, Antonella Capozza, Claudio Maioli, Andrea Luciani, Anna M Ierardi, Gianpaolo Carrafiello
Since the beginning of second decade of this century, when it was introduced in many oncologic scenarios, immunotherapy has become an important tool in the management of a growing number of cancers. Engaging the host immune system in cancer therapy seems to be useful, improving not only progression free survival but also overall survival, until the achieving the goal that many advanced cancers, previously considered without effective treatment options, have now become successfully treatable. Moreover, considering the relatively recent introduction of these drugs in clinical scenarios and the continuous releasing of new drugs, large validated clinical experiences are lacking and many issues are today debated; by the way, the evaluation of the response to immune-therapy poses major concerns...
November 22, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29166668/interleukin-36%C3%AE-and-il-36-receptor-signaling-mediate-impaired-host-immunity-and-lung-injury-in-cytotoxic-pseudomonas-aeruginosa-pulmonary-infection-role-of-prostaglandin-e2
#2
Tetsuji Aoyagi, Michael W Newstead, Xianying Zeng, Yuta Nanjo, Marc Peters-Golden, Mitsuo Kaku, Theodore J Standiford
Pseudomonas aeruginosa is a Gram-negative pathogen that can lead to severe infection associated with lung injury and high mortality. The interleukin (IL)-36 cytokines (IL-36α, IL-36β and IL-36γ) are newly described IL-1 like family cytokines that promote inflammatory response via binding to the IL-36 receptor (IL-36R). Here we investigated the functional role of IL-36 cytokines in the modulating of innate immune response against P. aeruginosa pulmonary infection. The intratracheal administration of flagellated cytotoxic P...
November 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29166619/extensive-homeostatic-t-cell-phenotypic-variation-within-the-collaborative-cross
#3
Jessica B Graham, Jessica L Swarts, Michael Mooney, Gabrielle Choonoo, Sophia Jeng, Darla R Miller, Martin T Ferris, Shannon McWeeney, Jennifer M Lund
The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse strains with high levels of standing genetic variation, affording an unprecedented opportunity to perform experiments in a small animal model containing controlled genetic diversity while allowing for genetic replicates. Here, we advance the utility of this unique mouse resource for immunology research because it allows for both examination and genetic dissection of mechanisms behind adaptive immune states in mice with distinct and defined genetic makeups...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166616/the-aryl-hydrocarbon-receptor-preferentially-marks-and-promotes-gut-regulatory-t-cells
#4
Jian Ye, Ju Qiu, John W Bostick, Aki Ueda, Hilde Schjerven, Shiyang Li, Christian Jobin, Zong-Ming E Chen, Liang Zhou
The local environment may affect the development and function of tissue-resident T regulatory cells (Tregs), which are crucial for controlling inflammation. Although the aryl hydrocarbon receptor (Ahr), an environmental sensor, is expressed by Tregs, its role in Treg cell development and/or function remains elusive. Here, we generated mouse genetic models to ablate or activate Ahr expression specifically in Tregs. We showed that Ahr was expressed more abundantly by peripherally induced Tregs (pTregs) in the gut and that its expression was independent of microbiota...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166611/ccr5-directs-the-mobilization-of-cd11b-gr1-ly6c-low-polymorphonuclear-myeloid-cells-from-the-bone-marrow-to-the-blood-to-support-tumor-development
#5
Elias Hawila, Hila Razon, Gizi Wildbaum, Carolin Blattner, Yair Sapir, Yuval Shaked, Viktor Umansky, Nathan Karin
Cells of hematopoietic origin can be subdivided into cells of the lymphoid lineage and those of the myeloid lineage, among which are myeloid-derived suppressor cells (MDSCs). The MDSCs can be further divided into CD11b(+)Ly6G(-)Ly6C(hi) monocytic (Mo) MDSCs and CD11b(+)Ly6G(+)Ly6C(low) polymorphonuclear (PMN) MDSCs. Both subtypes support tumor growth and suppress anti-tumor immunity. Their accumulation at the tumor site includes mobilization from the bone marrow to the blood followed by colonization at the tumor site...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166591/a-cd103-conventional-dendritic-cell-surveillance-system-prevents-development-of-overt-heart-failure-during-subclinical-viral-myocarditis
#6
Xavier Clemente-Casares, Siyavash Hosseinzadeh, Iulia Barbu, Sarah A Dick, Jillian A Macklin, Yiming Wang, Abdul Momen, Crystal Kantores, Laura Aronoff, Maylis Farno, Tiffany M Lucas, Joan Avery, Dorrin Zarrin-Khat, Heidi J Elsaesser, Babak Razani, Kory J Lavine, Mansoor Husain, David G Brooks, Clinton S Robbins, Myron Cybulsky, Slava Epelman
Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103(+) and CD11b(+), which differentially relied on local proliferation and precursor recruitment to maintain their tissue residency. Following viral infection of the myocardium, cDCs accumulated in the heart coincident with monocyte infiltration and loss of resident reparative embryonic-derived cardiac macrophages...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166590/interleukin-33-activated-islet-resident-innate-lymphoid-cells-promote-insulin-secretion-through-myeloid-cell-retinoic-acid-production
#7
Elise Dalmas, Frank M Lehmann, Erez Dror, Stephan Wueest, Constanze Thienel, Marcela Borsigova, Marc Stawiski, Emmanuel Traunecker, Fabrizio C Lucchini, Dianne H Dapito, Sandra M Kallert, Bruno Guigas, Francois Pattou, Julie Kerr-Conte, Pierre Maechler, Jean-Philippe Girard, Daniel Konrad, Christian Wolfrum, Marianne Böni-Schnetzler, Daniela Finke, Marc Y Donath
Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1β, and palmitate). IL-33 promoted β cell function through islet-resident group 2 innate lymphoid cells (ILC2s) that elicited retinoic acid (RA)-producing capacities in macrophages and dendritic cells via the secretion of IL-13 and colony-stimulating factor 2...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166588/regulatory-t-cell-migration-is-dependent-on-glucokinase-mediated-glycolysis
#8
Madhav Kishore, Kenneth C P Cheung, Hongmei Fu, Fabrizia Bonacina, Guosu Wang, David Coe, Eleanor J Ward, Alessandra Colamatteo, Maryam Jangani, Andrea Baragetti, Giuseppe Matarese, David M Smith, Robert Haas, Claudio Mauro, David C Wraith, Klaus Okkenhaug, Alberico L Catapano, Veronica De Rosa, Giuseppe D Norata, Federica M Marelli-Berg
Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK)...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166587/migrating-myeloid-cells-sense-temporal-dynamics-of-chemoattractant-concentrations
#9
Caren E Petrie Aronin, Yun M Zhao, Justine S Yoon, Nicole Y Morgan, Thorsten Prüstel, Ronald N Germain, Martin Meier-Schellersheim
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166586/the-broad-spectrum-of-human-natural-killer-cell-diversity
#10
REVIEW
Aharon G Freud, Bethany L Mundy-Bosse, Jianhua Yu, Michael A Caligiuri
Natural killer (NK) cells provide protection against infectious pathogens and cancer. For decades it has been appreciated that two major NK cell subsets (CD56(bright) and CD56(dim)) exist in humans and have distinct anatomical localization patterns, phenotypes, and functions in immunity. In light of this traditional NK cell dichotomy, it is now clear that the spectrum of human NK cell diversity is much broader than originally appreciated as a result of variegated surface receptor, intracellular signaling molecule, and transcription factor expression; tissue-specific imprinting; and foreign antigen exposure...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166583/the-skinny-pancreatic-ilc2s-promote-insulin-secretion
#11
Kelly M Cautivo, Ari B Molofsky
Regulation of pancreatic insulin production is pivotal in the pathophysiology and treatment of diabetes. In this issue of Immunity, Dalmas et al. (2017) describe a type 2 immune circuit where pancreatic interleukin-33 (IL-33) promotes insulin secretion via the activity of islet-associated group 2 innate lymphoid cells (ILC2s).
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166582/the-silent-undertakers-macrophages-programmed-for-efferocytosis
#12
Judith E Allen, Dominik Rückerl
Two recent Immunity papers provide new insight into efferocytosis by tissue-resident macrophages. Baratin et al. (2017) identify a resident macrophage population in the T cell zone of lymph nodes responsible for the silent uptake of vast numbers of apoptotic cells. Roberts et al. (2017) find that resident macrophages can be programmed by local tissue signals not to respond to the nucleic acid of apoptotic cells.
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166580/a-sweet-solution-glycolysis-dependent-treg-cell-migration
#13
Ronen Alon
mTORC2 is a metabolic regulatory complex activated by PI3K. In this issue of Immunity, Kishore et al. (2017) demonstrate a specialized role for this complex in the migration of regulatory T (Treg) cells to sites of inflammation rather than their differentiation and survival.
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166579/the-tcr-takes-some-immune-responsibility
#14
Ashley A Viehmann Milam, Paul M Allen
In this issue of Immunity, Van Braeckel-Budimmir et al. (2017) reveal that the pathogenic response of mice to a Plasmodium berghei infection is dominated by a Vβ8.1 T cell response. Mice lacking Vβ8.1 T cells fail to mount a pathogenic response, thus showing that the TCR locus can be an Immune response (Ir) gene.
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal-%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#15
Gunhyuk Park, Seoung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal(®)) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and auto-immune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor (TNF)-α inhibitor to the treatment can be beneficial...
November 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29166568/camel-whey-protein-protects-lymphocytes-from-apoptosis-via-the-pi3k-akt-nf-%C3%AE%C2%BAb-atf-3-and-hsp-70-signaling-pathways-in-heat-stressed-male-mice
#16
Gamal Badr, Nancy K Ramadan, Hanem S Abdel-Tawab, Samia F Ahmed, Mohamed H Mahmoud
Heat stress (HS) is an environmental factor that depresses the immune systems mediating dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. The present study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were divided into three groups: control group; HS group; and HS mice that were orally administered CWP (HS+CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) as well as a significant reduction in the IL-2 and IL-4 levels...
November 22, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29166179/imbalance-between-subpopulations-of-regulatory-t-cells-in-patients-with-acute-exacerbation-of-copd
#17
Xia Yang, Bo Huo, Xiaoning Zhong, Wenyan Su, Wenting Liu, Yumei Li, Zhiyi He, Jing Bai
Human regulatory T cells (Tregs) have been reported to be not significantly different in the peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Recent research has identified some new markers for Tregs and indicated that Tregs are composed of distinct subpopulations. The aim of the study was to describe the changing patterns of circulating Treg subpopulations in patients with acute exacerbation of COPD (AECOPD) and healthy controls, and to explore their potential roles in AECOPD pathogenesis...
November 22, 2017: COPD
https://www.readbyqxmd.com/read/29166136/the-gamma-aminobutyric-acid-b-receptor-gabab-encephalitis-clinical-manifestations-and-response-to-immunotherapy
#18
Junzhao Cui, Hui Bu, Junying He, Zeyan Zhao, Weixin Han, Ruiping Gao, Xiaoqing Li, Qing Li, Xiaosu Guo, Yueli Zou
PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyse the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Seven of the eleven patients were males, and a mean age at presentation of 63 years (range: 47-79 years)...
November 22, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29165988/bioconjugate-strategies-for-the-induction-of-antigen-specific-tolerance-in-autoimmune-diseases
#19
Chunsong Yu, Jingchao Xi, Meng Li, Myunggi An, Haipeng Liu
Antigen-specific immunotherapy (ASI) holds great promise for the treatment of autoimmune diseases. In mice, administration of major histocompatibility complex (MHC) binding synthetic peptides which modulate T cell receptor (TCR) signaling under subimmunogenic conditions induces selective tolerance without suppressing the global immune responses. However, clinical translation has yielded limited success. It has become apparent that the TCR signaling pathway via synthetic peptide antigen alone is inadequate to induce an effective tolerogenic immunity in autoimmune diseases...
November 22, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29165740/platelets-as-modulators-of-inflammation
#20
Seok-Joo Kim, Rachelle P Davis, Craig N Jenne
Platelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify immune and endothelial cell responses. Increased platelet activity can protect the host against infectious insults; however, the excessive activity can lead to inflammation-mediated tissue damage...
November 17, 2017: Seminars in Thrombosis and Hemostasis
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