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https://www.readbyqxmd.com/read/28654060/functional-characterization-of-regulatory-macrophages-that-inhibit-graft-reactive-immunity
#1
Jordi Ochando, Patricia Conde
Macrophage accumulation in transplanted organs has long been recognized as a feature of allograft rejection(1). Immunogenic monocytes infiltrate the allograft early after transplantation, mount a graft reactive response against the transplanted organ, and initiate organ rejection(2). Recent data suggest that suppressive macrophages facilitate successful long-term transplantation(3) and are required for the induction of transplantation tolerance(4). This suggests a multidimensional concept of macrophage ontogeny, activation, and function, which demands a new roadmap for the isolation and analysis of macrophage function(5)...
June 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28652399/c-rel-and-i%C3%AE%C2%BAbns-govern-common-and-independent-steps-of-regulatory-t-cell-development-from-novel-cd122-expressing-pre-precursors
#2
Marc Schuster, Carlos Plaza-Sirvent, Anne-Marie Matthies, Ulrike Heise, Andreas Jeron, Dunja Bruder, Alexander Visekruna, Jochen Huehn, Ingo Schmitz
Foxp3-expressing regulatory T cells (Tregs) are essential regulators of immune homeostasis and, thus, are prime targets for therapeutic interventions of diseases such as cancer and autoimmunity. c-REL and IκBNS are important regulators of Foxp3 induction in Treg precursors upon γ-chain cytokine stimulation. In c-REL/IκBNS double-deficient mice, Treg numbers were dramatically reduced, indicating that together, c-REL and IκBNS are pivotal for Treg development. However, despite the highly reduced Treg compartment, double-deficient mice did not develop autoimmunity even when aged to more than 1 y, suggesting that c-REL and IκBNS are required for T cell effector function as well...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652179/non-coding-rna-regulation-of-t-cell-biology-implications-for-age-associated-cardiovascular-diseases
#3
REVIEW
Jose Coelho-Lima, Ioakim Spyridopoulos
Prevalence of age-associated cardiovascular diseases (CVD) has dramatically increased as a result of improvements in life expectancy. Chronic inflammation is a shared pathophysiological feature of age-associated CVDs, indicating a role for the immune system in the onset and development of CVDs. Indeed, ageing elicits profound changes in both the cardiovascular and immune system, especially in the T cell compartment. Although such changes have been well described at the cellular level, the molecular mechanisms underlying immune-mediated cardiovascular ageing remain largely unexplored...
June 23, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28651742/strap-positively-regulates-tlr3-triggered-signaling-pathway
#4
Hyunbin D Huh, Eunhye Lee, Jinwook Shin, Boyoun Park, Sungwook Lee
Toll-like receptor (TLR) signaling drives the innate immune response by activating nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF). We have previously shown that STRAP interacts with TAK1 and IKKα along with NF-κB subunit p65, leading to the activation of pro-inflammatory cytokines. However, the roles of STRAP in TRIF/TBK1-mediated TLR3 activation and the subsequent type I interferon (IFN) production are not fully elucidated. Here, we demonstrate that STRAP acts as a scaffold protein in TLR3-triggered signaling...
June 19, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28651566/arginine-kinase-from-haemonchus-contortus-decreased-the-proliferation-and-increased-the-apoptosis-of-goat-pbmcs-in-vitro
#5
Muhammad Ehsan, WenXiang Gao, Javaid Ali Gadahi, MingMin Lu, XinChao Liu, YuJian Wang, RuoFeng Yan, LiXin Xu, XiaoKai Song, XiangRui Li
BACKGROUND: Arginine kinase (AK), an important member of phosphagen kinase family has been extensively studied in various vertebrates and invertebrates. Immunologically, AKs are important constituents of different body parts, involved in various biological and cellular functions, and considered as immune-modulator and effector for pro-inflammatory cytokines. However, immunoregulatory changes of host cells triggered by AK protein of Haemonchus contortus, a parasitic nematode of ruminants, are still unknown...
June 26, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28651073/hemophilia-a-inhibitor-treatment-the-promise-of-engineered-t-cell-therapy
#6
REVIEW
Kalpana Parvathaneni, Maha Abdeladhim, Kathleen P Pratt, David W Scott
Hemophilia A is a bleeding disorder caused by mutations in the gene encoding factor VIII (FVIII), a cofactor protein that is essential for normal blood clotting. Approximately, 1 in 3 patients with severe hemophilia A produce neutralizing antibodies (inhibitors) that block its biologic function in the clotting cascade. Current efforts to eliminate inhibitors consist of repeated FVIII injections under what is termed an "ITI" protocol (Immune Tolerance Induction). However, this method is extremely costly and approximately 30% of patients undergoing ITI do not achieve peripheral tolerance...
June 9, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28650992/galectin-8-as-an-immunosuppressor-in-experimental-autoimmune-encephalomyelitis-and-a-target-of-human-early-prognostic-antibodies-in-multiple-sclerosis
#7
Evelyn Pardo, Claudia Cárcamo, Reinaldo Uribe-San Martín, Ethel Ciampi, Fabián Segovia-Miranda, Cristobal Curkovic-Peña, Fabián Montecino, Christopher Holmes, Juan Enrique Tichauer, Eric Acuña, Francisco Osorio-Barrios, Marjorie Castro, Priscilla Cortes, Claudia Oyanadel, David M Valenzuela, Rodrigo Pacheco, Rodrigo Naves, Andrea Soza, Alfonso González
Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients...
2017: PloS One
https://www.readbyqxmd.com/read/28649982/structural-and-regulatory-diversity-shape-hla-c-protein-expression-levels
#8
Gurman Kaur, Stephanie Gras, Jesse I Mobbs, Julian P Vivian, Adrian Cortes, Thomas Barber, Subita Balaram Kuttikkatte, Lise Torp Jensen, Kathrine E Attfield, Calliope A Dendrou, Mary Carrington, Gil McVean, Anthony W Purcell, Jamie Rossjohn, Lars Fugger
Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28649760/immunometabolism-of-human-autoimmune-diseases-from-metabolites-to-extracellular-vesicles
#9
REVIEW
Paola de Candia, Veronica De Rosa, Vincenzo Gigantino, Gerardo Botti, Antonio Ceriello, Giuseppe Matarese
Immunometabolism focuses on the mechanisms regulating the impact of metabolism on lymphocyte activity and autoimmunity outbreak. The adipose tissue is long known to release adipokines, either pro- or anti-inflammatory factors bridging nutrition and immune function. More recently, adipocytes were discovered to also release extracellular vesicles (EVs) containing a plethora of biological molecules, including metabolites and microRNAs, which can regulate cell function/metabolism in distant tissues, suggesting that immune regulatory function by the adipose tissue may be far more complex than originally thought...
June 26, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28649611/lrrk2-levels-in-immune-cells-are-increased-in-parkinson-s-disease
#10
D A Cook, G T Kannarkat, A F Cintron, Laura M Butkovich, Kyle B Fraser, J Chang, N Grigoryan, S A Factor, Andrew B West, J M Boss, M G Tansey
Mutations associated with leucine-rich repeat kinase 2 are the most common known cause of Parkinson's disease. The known expression of leucine-rich repeat kinase 2 in immune cells and its negative regulatory function of nuclear factor of activated T cells implicates leucine-rich repeat kinase 2 in the development of the inflammatory environment characteristic of Parkinson's disease. The aim of this study was to determine the expression pattern of leucine-rich repeat kinase 2 in immune cell subsets and correlate it with the immunophenotype of cells from Parkinson's disease and healthy subjects...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649610/evaluation-of-the-safety-and-immunomodulatory-effects-of-sargramostim-in-a-randomized-double-blind-phase-1-clinical-parkinson-s-disease-trial
#11
Howard E Gendelman, Yuning Zhang, Pamela Santamaria, Katherine E Olson, Charles R Schutt, Danish Bhatti, Bhagya Laxmi Dyavar Shetty, Yaman Lu, Katherine A Estes, David G Standaert, Elizabeth Heinrichs-Graham, LuAnn Larson, Jane L Meza, Matthew Follett, Erica Forsberg, Gary Siuzdak, Tony W Wilson, Carolyn Peterson, R Lee Mosley
A potential therapeutic role for immune transformation in Parkinson's disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson's disease patients...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649440/cross-species-gene-modules-emerge-from-a-systems-biology-approach-to-osteoarthritis
#12
Alan James Mueller, Elizabeth G Canty-Laird, Peter D Clegg, Simon R Tew
Complexities in degenerative disorders, such as osteoarthritis, arise from multiscale biological, environmental, and temporal perturbations. Animal models serve to provide controlled representations of the natural history of degenerative disorders, but in themselves represent an additional layer of complexity. Comparing transcriptomic networks arising from gene co-expression data across species can facilitate an understanding of the preservation of functional gene modules and establish associations with disease phenotypes...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28649380/gitr-ligand-fusion-protein-agonist-enhances-the-tumor-antigen-specific-cd8-t-cell-response-and-leads-to-long-lasting-memory
#13
Nick M Durham, Nick Holoweckyj, Randall S MacGill, Kelly McGlinchey, Ching Ching Leow, Scott H Robbins
BACKGROUND: The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations. METHODS: We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28649127/the-novel-%C3%AE-glucan-ycp-improves-the-survival-rates-and-symptoms-in-septic-mice-by-regulating-myeloid-derived-suppressor-cells
#14
Dan Liu, Ming You, Guang-Feng Zhao, Xiu-Jun Li, Yu-Xian Song, Huan Dou, Wen-Bing Yao, Xiang-Dong Gao, Ya-Yi Hou
Sepsis is a life-threatening health condition that is initially characterized by uncontrolled inflammation, followed by the development of persistent immunosuppression. YCP is a novel α-glucan purified from the mycelium of the marine fungus Phoma herbarum YS4108, which has displayed strong antitumor activity via enhancing host immune responses. In this study, we investigated whether YCP could influence the development of sepsis in a mouse model. Caecal ligation and puncture (CLP)-induced sepsis was established in mice that were treated with YCP (20 mg/kg, ip or iv) 2 h before, 4 and 24 h after the CLP procedure, and then every other day...
June 26, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28648331/il-35-as-a-newly-proposed-homeostasis-associated-molecular-pattern-plays-three-major-functions-including-anti-inflammatory-initiator-effector-and-blocker-in-cardiovascular-diseases
#15
Xinyuan Li, Pu Fang, William Y Yang, Hong Wang, Xiaofeng Yang
IL-35 is a new anti-inflammatory cytokine identified in 2007, which inhibits inflammation and immune responses by inducing regulatory T cells and regulatory B cells and suppressing effector T cells and macrophages. The unique initiator and effector anti-inflammatory properties of IL-35 bring tremendous interest in investigating its role during cardiovascular disease (CVD) development, in which inflammatory processes are firmly established as central to its development and complications. In this review, we update recent understanding of how IL-35 is produced and regulated in the cells...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28647573/focal-adhesion-kinase-signaling-regulates-anti-inflammatory-function-of-bone-marrow-mesenchymal-stromal-cells-induced-by-biomechanical-force
#16
Hyun Jung Lee, Miguel F Diaz, Adesuwa Ewere, Scott D Olson, Charles S Cox, Pamela L Wenzel
Mesenchymal stromal cells (MSCs) have tremendous potential for use in regenerative medicine due to their multipotency and immune cell regulatory functions. Biomimetic physical forces have been shown to direct differentiation and maturation of MSCs in tissue engineering applications; however, the effect of force on immunomodulatory activity of MSCs has been largely overlooked. Here we show in human bone marrow-derived MSCs that wall shear stress (WSS) equivalent to the fluid frictional force present in the adult arterial vasculature significantly enhances expression of four genes that mediate MSC immune regulatory function, PTGS2, HMOX1, IL1RN, and TNFAIP6...
June 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28647398/immune-modulatory-effects-of-syncytiotrophoblast-extracellular-vesicles-in-pregnancy-and-preeclampsia
#17
Claudia Göhner, Torsten Plösch, Marijke M Faas
Unique immunologic adaptations exist to successfully establish and maintain pregnancy and to avoid an immune attack against the semi allogenic fetus. These adaptations occur both locally at the maternofetal interface and in the peripheral circulation and affect the innate as well as the adaptive immune system. Pregnancy is characterized by a general inflammatory state with activation of monocytes and granulocytes, but also with suppressive lymphocytes (regulatory T cells), and skewing towards T helper 2 immunity...
June 7, 2017: Placenta
https://www.readbyqxmd.com/read/28646912/influences-of-age-related-changes-in-mesenchymal-stem-cells-on-macrophages-during-in-vitro-culture
#18
Yuan Yin, Rui-Xin Wu, Xiao-Tao He, Xin-Yue Xu, Jia Wang, Fa-Ming Chen
BACKGROUND: Mesenchymal stem cells (MSCs) have been widely used in cytotherapy and tissue engineering due to their immunosuppressive ability and regenerative potential. Recently, the immunomodulatory influence of MSCs has been gaining increasing attention because their functional roles in modulating immune responses likely have high clinical significance. METHODS: In this study, we investigated the influence of MSCs on macrophages (Mφs) in in-vitro cell culture systems...
June 24, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#19
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28646041/concurrent-ox40-and-cd30-ligand-blockade-abrogates-the-cd4-driven-autoimmunity-associated-with-ctla4-and-pd1-blockade-while-preserving-excellent-anti-cd8-tumor-immunity
#20
Maher G Nawaf, Maria H Ulvmar, David R Withers, Fiona M McConnell, Fabrina M Gaspal, Gwilym J Webb, Nick D Jones, Hideo Yagita, James P Allison, Peter J L Lane
Although strategies that block FOXP3-dependent regulatory T cell function (CTLA4 blockade) and the inhibitory receptor PD1 have shown great promise in promoting antitumor immune responses in humans, their widespread implementation for cancer immunotherapy has been hampered by significant off-target autoimmune side effects that can be lethal. Our work has shown that absence of OX40 and CD30 costimulatory signals prevents CD4 T cell-driven autoimmunity in Foxp3-deficient mice, suggesting a novel way to block these side effects...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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