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https://www.readbyqxmd.com/read/28807240/role-of-exosomes-in-treatment-of-hepatocellular-carcinoma
#1
REVIEW
Demetrios Moris, Eliza W Beal, Jeffery Chakedis, Richard A Burkhart, Carl Schmidt, Mary Dillhoff, Xufeng Zhang, Stamatios Theocharis, Timothy M Pawlik
Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC...
September 2017: Surgical Oncology
https://www.readbyqxmd.com/read/28805019/cd11b-gr1-dim-tolerogenic-dendritic-cell-like-cells-are-expanded-in-interstitial-lung-disease-in-skg-mice
#2
Sho Sendo, Jun Saegusa, Takaichi Okano, Soshi Takahashi, Kengo Akashi, Akio Morinobu
OBJECTIVE: SKG mice develop interstitial lung disease (ILD) resembling rheumatoid arthritis-associated ILD (RA-ILD) in human. The aim of this study is to clarify the mechanism behind the lung pathology by analyzing the lung-infiltrating cells in ILD of SKG mice. METHODS: We assessed the severity of zymosan A (ZyA)-induced ILD in SKG mice histologically, and examined lung-infiltrating cells by flow cytometry. Total lung cells and isolated monocytic myeloid-derived suppressor cells (M-MDSCs) were cultured in vitro with GM-CSF (and IL-4)...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28804903/targeting-of-tolerogenic-dendritic-cells-towards-heat-shock-proteins-a-novel-therapeutic-strategy-for-autoimmune-diseases
#3
REVIEW
Manon A A Jansen, Rachel Spiering, Femke Broere, Jacob M van Laar, John D Isaacs, Willem van Eden, Catharien M U Hilkens
Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T cell response, while leaving other, protective T cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen...
August 14, 2017: Immunology
https://www.readbyqxmd.com/read/28794505/differential-transcriptome-of-tolerogenic-versus-inflammatory-dendritic-cells-points-to-modulated-t1d-genetic-risk-and-enriched-immune-regulation
#4
T Nikolic, N J C Woittiez, A van der Slik, S Laban, A Joosten, C Gysemans, C Mathieu, J J Zwaginga, B Koeleman, B O Roep
Tolerogenic dendritic cells (tolDCs) are assessed as immunomodulatory adjuvants to regulate autoimmunity. The underlying gene expression endorsing their regulatory features remains ill-defined. Using deep mRNA sequencing, we compared transcriptomes of 1,25-dihydroxyvitaminD3/dexametasone-modulated tolDCs with that of non-modulated mature inflammatory DCs (mDCs). Differentially expressed genes controlled cellular interactions, metabolic pathways and endorse tolDCs with the capacity to regulate cell activation through nutrient and signal deprivation, collectively gearing tolDCs into tolerogenic immune regulators...
August 10, 2017: Genes and Immunity
https://www.readbyqxmd.com/read/28793252/human-gut-derived-commensal-bacteria-suppress-cns-inflammatory-and-demyelinating-disease
#5
Ashutosh Mangalam, Shailesh K Shahi, David Luckey, Melissa Karau, Eric Marietta, Ningling Luo, Rok Seon Choung, Josephine Ju, Ramakrishna Sompallae, Katherine Gibson-Corley, Robin Patel, Moses Rodriguez, Chella David, Veena Taneja, Joseph Murray
The human gut is colonized by a large number of microorganisms (∼10(13) bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28792480/the-role-of-nutritional-aspects-in-food-allergy-prevention-and-management
#6
REVIEW
Alessandra Mazzocchi, Carina Venter, Kate Maslin, Carlo Agostoni
The prevalence of food allergy in childhood appears to be increasing in both developed and transitional countries. The aim of this paper is to review and summarise key findings in the prevention and management of food allergy, focusing on the role of dietary components and nutritional habits in the development and optimal functioning of the immune system. Essential fatty acids, zinc and vitamin D are likely to enhance the anti-inflammatory and antioxidative barrier and promote immunologic tolerance. Additionally, nutritional components such as pre- and probiotics represent a novel research approach in the attempt to induce a tolerogenic immune environment...
August 9, 2017: Nutrients
https://www.readbyqxmd.com/read/28791576/tolerogenic-nanoparticles-to-treat-islet-autoimmunity
#7
REVIEW
Tobias Neef, Stephen D Miller
PURPOSE OF REVIEW: The current standard therapy for type 1 diabetes (T1D) is insulin replacement. Autoimmune diseases are typically treated with broad immunosuppression, but this has multiple disadvantages. Induction of antigen-specific tolerance is preferable. The application of nanomedicine to the problem of T1D can take different forms, but one promising way is the development of tolerogenic nanoparticles, the aim of which is to mitigate the islet-destroying autoimmunity. We review the topic and highlight recent strategies to produce tolerogenic nanoparticles for the purpose of treating T1D...
August 8, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28791025/the-ido-ahr-axis-controls-th17-treg-immunity-in-a-pulmonary-model-of-fungal-infection
#8
Eliseu Frank de Araújo, Claudia Feriotti, Nayane Alves de Lima Galdino, Nycolas Willian Preite, Vera Lúcia Garcia Calich, Flávio Vieira Loures
In infectious diseases, the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) that catalyzes the tryptophan (Trp) degradation along the kynurenines (Kyn) pathway has two main functions, the control of pathogen growth by reducing available Trp and immune regulation mediated by the Kyn-mediated expansion of regulatory T (Treg) cells via aryl hydrocarbon receptor (AhR). In pulmonary paracoccidioidomycosis (PCM) caused by the dimorphic fungus Paracoccidioides brasiliensis, IDO1 was shown to control the disease severity of both resistant and susceptible mice to the infection; however, only in resistant mice, IDO1 is induced by TGF-β signaling that confers a stable tolerogenic phenotype to dendritic cells (DCs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28775118/chronic-lymphocytic-leukemia-cells-are-active-participants-in-microenvironmental-cross-talk
#9
Martijn Ha van Attekum, Eric Eldering, Arnon P Kater
The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Yet, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Whereas numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment by engaging in several cross-talk mechanisms...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28772190/an-antigen-specific-semi-therapeutic-treatment-with-local-delivery-of-tolerogenic-factors-through-a-dual-sized-microparticle-system-blocks-experimental-autoimmune-encephalomyelitis
#10
Jonathan J Cho, Joshua M Stewart, Theodore T Drashansky, Maigan A Brusko, Ashley N Zuniga, Kyle J Lorentsen, Benjamin G Keselowsky, Dorina Avram
Antigen-specific treatments are highly desirable for autoimmune diseases in contrast to treatments which induce systemic immunosuppression. A novel antigen-specific therapy has been developed which, when administered semi-therapeutically, is highly efficacious in the treatment of the mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). The treatment uses dual-sized, polymeric microparticles (dMPs) loaded with specific antigen and tolerizing factors for intra- and extra-cellular delivery, designed to recruit and modulate dendritic cells toward a tolerogenic phenotype without systemic release...
July 24, 2017: Biomaterials
https://www.readbyqxmd.com/read/28766556/antigen-specific-regulatory-t-cell-responses-to-intestinal-microbiota
#11
REVIEW
E V Russler-Germain, S Rengarajan, C-S Hsieh
The mammalian gastrointestinal tract can harbor both beneficial commensal bacteria important for host health, but also pathogenic bacteria capable of intestinal damage. It is therefore important that the host immune system mount the appropriate immune response to these divergent groups of bacteria-promoting tolerance in response to commensal bacteria and sterilizing immunity in response to pathogenic bacteria. Failure to induce tolerance to commensal bacteria may underlie immune-mediated diseases such as human inflammatory bowel disease...
August 2, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28765071/ficz-generates-human-tdcs-that-induce-cd4-cd25-high-foxp3-treg-like-cell-differentiation
#12
Brenda B Jurado-Manzano, Daniel Zavala-Reyes, Edgar A Turrubiartes-Martínez, Diana P Portales-Pérez, Roberto González-Amaro, Esther Layseca-Espinosa
Dendritic cells (DCs) play a central role in the maintenance of immune homeostasis, their participation as professional antigen presenting cells is essential to the initiation of the adaptive immune response as well as to the induction of tolerance. The recently described role of the aryl hydrocarbon receptor (AhR) in the immune system, particularly in the modulation of the adaptive immune response has attracted the attention as a potential player in the induction of immune tolerance. However, the effects of AhR activation through endogenous ligands on human DCs have been poorly evaluated...
July 29, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28763794/targeting-latency-associated-peptide-promotes-antitumor-immunity
#13
Galina Gabriely, Andre P da Cunha, Rafael M Rezende, Brendan Kenyon, Asaf Madi, Tyler Vandeventer, Nathaniel Skillin, Stephen Rubino, Lucien Garo, Maria A Mazzola, Panagiota Kolypetri, Amanda J Lanser, Thais Moreira, Ana Maria C Faria, Hans Lassmann, Vijay Kuchroo, Gopal Murugaiyan, Howard L Weiner
Regulatory T cells (Tregs) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on Tregs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP(+) Tregs, tolerogenic dendritic cells, and TGF-β secretion and is associated with CD8(+) T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8(+) T cells and reduces CD103(+) CD8 T cells in draining lymph nodes and the spleen...
May 19, 2017: Science Immunology
https://www.readbyqxmd.com/read/28763099/autologous-tolerogenic-dendritic-cells-derived-from-monocytes-of-systemic-lupus-erythematosus-patients-and-healthy-donors-show-a-stable-and-immunosuppressive-phenotype
#14
Javiera Obreque, Fabián Vega, Andy Torres, Loreto Cuitino, Juan P Mackern-Oberti, Paola Viviani, Alexis Kalergis, Carolina Llanos
Systemic Lupus Erythematosus (SLE) is an autoimmune disease with unrestrained T-cell and B cell activity towards self-antigens. Evidence shows that apoptotic cells (ApoCells) trigger an autoreactive response against nuclear antigens in susceptible individuals. In this study, we focus on generating and characterizing tolerogenic dendritic cells (tolDCs) to restore tolerance to ApoCells. Monocyte-derived dendritic cells (DCs) from healthy controls (HC) and SLE patients were treated with dexamethasone (DEXA) and rosiglitazone (RGZ) to induce tolDCs...
August 1, 2017: Immunology
https://www.readbyqxmd.com/read/28760498/differences-and-similarities-between-sublingual-immunotherapy-of-allergy-and-oral-tolerance
#15
REVIEW
Philippe Moingeon, Laurent Mascarell
Allergen immunotherapy is the only treatment altering the natural course of IgE-mediated allergies. Whereas the subcutaneous route for immunotherapy (SCIT) has been historically considered as a reference, we discuss herein the relative advantages of the sublingual and oral routes as alternatives to SCIT in order to elicit allergen-specific tolerance. The buccal and gut immune systems are similarly organized to favor immune tolerance to antigens/allergens, due to the presence of tolerogenic dendritic cells and macrophages promoting the differentiation of CD4(+) regulatory T cells...
July 28, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28759565/low-doses-of-cholera-toxin-and-its-mediator-camp-induce-ctla-2-secretion-by-dendritic-cells-to-enhance-regulatory-t-cell-conversion
#16
Cinthia Silva-Vilches, Katrien Pletinckx, Miriam Lohnert, Vladimir Pavlovic, Diyaaeldin Ashour, Vini John, Emilia Vendelova, Susanne Kneitz, Jie Zhou, Rena Chen, Thomas Reinheckel, Thomas D Mueller, Jochen Bodem, Manfred B Lutz
Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3+ induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CThi, CTlo) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β)...
2017: PloS One
https://www.readbyqxmd.com/read/28754680/versican-derived-matrikines-regulate-batf3-dendritic-cell-differentiation-and-promote-t-cell-infiltration-in-colorectal-cancer
#17
Chelsea Hope, Philip B Emmerich, Athanasios Papadas, Adam Pagenkopf, Kristina A Matkowskyj, Dana R Van De Hey, Susan N Payne, Linda Clipson, Natalie S Callander, Peiman Hematti, Shigeki Miyamoto, Michael G Johnson, Dustin A Deming, Fotis Asimakopoulos
Colorectal cancer originates within immunologically complex microenvironments. To date, the benefits of immunotherapy have been modest, except in neoantigen-laden mismatch repair-deficient tumors. Approaches to enhance tumor-infiltrating lymphocytes in the tumor bed may substantially augment clinical immunotherapy responses. In this article, we report that proteolysis of the tolerogenic matrix proteoglycan versican (VCAN) strongly correlated with CD8(+) T cell infiltration in colorectal cancer, regardless of mismatch repair status...
July 28, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28732440/intravenous-injection-of-myelin-oligodendrocyte-glycoprotein-coated-plga-microparticles-have-tolerogenic-effects-in-experimental-autoimmune-encephalomyelitis
#18
Mehrdad Gholamzad, Masoumeh Ebtekar, Mehdi Shafiee Ardestani
The abnormal function of the T lymphocytes causes a range of autoimmune diseases, particularly multiple sclerosis; hence, several methods have been used to treat these disorders through the induction of antigen-specific tolerance in T cells. The present study aims to use a simple and low-cost method to produce poly (lactic-co-glycolic acid) (PLGA) nanoparticles for carrying antigens and inducing antigen-specific tolerance. In this study, PLGA nanoparticles were produced using the water/oil/water (W/O/W) method...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28727997/therapeutic-intranasal-instillation-of-allergen-loaded-microbubbles-suppresses-experimental-allergic-asthma-in-mice
#19
Blaise Corthésy, Gilles Bioley
Despite proven efficiency, subcutaneous immunotherapy for aeroallergens is impaired by the duration of the protocol, the repeated injections and potential side-effects associated with the doses of allergen administered. Intranasal delivery of immunotherapeutic agents may overcome several of these drawbacks, provided that an efficient allergen delivery vehicle can be identified. This study evaluates whether intranasally delivered gas-filled microbubble (MB)-associated ovalbumin (OVA), used as a model allergen, can serve as a therapeutic treatment in a mouse model of established allergic asthma...
October 2017: Biomaterials
https://www.readbyqxmd.com/read/28723551/understanding-immunosuppression-after-sepsis
#20
Fatemeh Fattahi, Peter A Ward
Following a severe primary infection or trauma, the risk of developing pneumonia increases due to acquired immune defects collectively known as sepsis-induced immunosuppression. In this issue of Immunity, Roquilly et al. (2017) show that dendritic cells and macrophages developing in the lung after the resolution of a severe infection acquire tolerogenic properties that contribute to persistent immunosuppression and susceptibility to secondary infections.
July 18, 2017: Immunity
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