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https://www.readbyqxmd.com/read/28344998/low-dose-liver-targeted-gene-therapy-for-pompe-disease-enhances-therapeutic-efficacy-of-ert-via-immune-tolerance-induction
#1
Sang-Oh Han, Giuseppe Ronzitti, Benjamin Arnson, Christian Leborgne, Songtao Li, Federico Mingozzi, Dwight Koeberl
Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10(11) vector genomes [vg]/kg)...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28342908/intestinal-dendritic-cell-licensing-through-tlr4-is-required-for-oral-tolerance-in-allergic-contact-dermatitis
#2
Feriel Hacini-Rachinel, Mercedes Gomez de Agüero, Reem Kanjarawi, Ludovic Moro-Sibilot, Jean-Benoit Le Luduec, Claire Macari, Gilles Boschetti, Emilie Bardel, Philippe Langella, Bertrand Dubois, Dominique Kaiserlian
BACKGROUND: Induction of oral tolerance to haptens is an efficient way to prevent allergic contact dermatitis (ACD) in mice. Toll-like receptor (TLRs)-mediated sensing of the microbiota contributes to gut homeostasis, yet whether it contributes to induction of oral tolerance has not been documented. OBJECTIVE: We examined whether oral tolerance to the contact sensitizer DNFB depends on microbiota/TLRs and evaluated the role of TLR4 on the tolerogenic function of intestinal dendritic cells (DCs)...
March 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28337224/gut-mesenchymal-stromal-cells-in-immunity
#3
REVIEW
Valeria Messina, Carla Buccione, Giulia Marotta, Giovanna Ziccheddu, Michele Signore, Gianfranco Mattia, Rossella Puglisi, Benedetto Sacchetti, Livia Biancone, Mauro Valtieri
Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal)...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28323492/regulatory-and-exhausted-t-cell-responses-to-aav-capsid
#4
Gwladys Gernoux, James M Wilson, Christian Mueller
Recombinant adeno-associated viruses are quickly becoming the preferred viral vector for viral gene delivery for the treatment of a wide variety of genetic disorders. However, since their use in a clinical trial targeting Hemophilia B patients 10 years ago, immune responses to AAV capsid appear to have hampered some of the early clinical gene transfer efficacy. Indeed, AAV-based gene transfer has been shown to reactivate capsid-specific memory T cells which have correlated with a decline in AAV transduced tissue in some patients...
March 21, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28321216/facilitated-peptide-transport-via-the-mucosal-epithelium-impact-on-tolerance-induction
#5
Elisabeth E Kenngott, Jennifer Pfeil, Ute Hoffmann, Uta Lauer, Anja A Kühl, Anne Rigby, Anton Pernthaner, Alf Hamann
A hallmark of autoimmunity is the breakdown of tolerance and generation of effector responses against self-antigens. Re-establishment of tolerance in autoimmune disorders was always the most desired treatment option; however, despite many efforts, clinical trials have been largely unsuccessful. This also applies to the generation of oral tolerance, which seems to be a default response type of the mucosa-associated lymphoid tissues to harmless antigens. In this study, we report improved efficacy of oral tolerance induction by coupling antigen with the newly identified mucosal carrier peptide 13C...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28294313/suppression-of-murine-tumor-growth-through-cd8-ctls-via-activated-dec-205-dendritic-cells-by-sequential-administration-of-%C3%AE-galactosylceramide-in-vivo
#6
Hideki Kogo, Masumi Shimizu, Yasuyuki Negishi, Eiji Uchida, Hidemi Takahashi
Cancer immunity is mediated through the effective priming and activation of tumor-specific class I major histocompatibility complex (MHC-I) molecule-restricted CD8(+) cytotoxic T lymphocytes (CTLs). DEC-205(+) dendritic cells (DCs) can cross-present the epitope(s) of captured tumor antigens associated with class I MHC molecules alongside co-stimulatory molecules to prime and activate tumor-specific CD8(+) CTLs. Immunosuppressive tolerogenic DCs with reduced co-stimulatory molecules may be a cause of impaired CTL induction...
March 12, 2017: Immunology
https://www.readbyqxmd.com/read/28293930/anti-interleukin-9-antibody-increases-the-effect-of-allergen-specific-immunotherapy-in-murine-allergic-rhinitis
#7
Ji Hyeon Shin, Do Hyun Kim, Boo Young Kim, Sung Won Kim, Se Hwan Hwang, Joohyung Lee, Soo Whan Kim
PURPOSE: Interleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR). METHODS: BALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28286106/regulatory-immune-cells-and-functions-in-autoimmunity-and-transplantation-immunology
#8
REVIEW
Gabor Papp, Peter Boros, Britt Nakken, Peter Szodoray, Margit Zeher
In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected...
March 7, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28282624/immunotoxicity-of-organophosphate-flame-retardants-tphp-and-tdcipp-on-murine-dendritic-cells-in%C3%A2-vitro
#9
Derya Canbaz, Adrian Logiantara, Ronald van Ree, Leonie S van Rijt
Organophosphate flame retardants (PFRs) are commonly used as alternatives for the banned polybrominated diphenyl ethers (PBDEs) and are ubiquitously detected in indoor dust. PFRs can be potentially hazardous to respiratory health via the inhalation of house dust. Dendritic cells (DCs) are crucial in the immunological defense against pathogens in the airways. In respiratory allergy however, an aberrant immune response is induced against innocuous proteins, like house dust mite allergens. In this study, we examined whether exposure to PFRs Triphenylphosphate (TPHP) and Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) affected activation/maturation of DCs at steady state and during exposure to house dust mite allergens (HDM)...
February 28, 2017: Chemosphere
https://www.readbyqxmd.com/read/28280691/old-game-new-players-linking-classical-theories-to-new-trends-in-transplant-immunology
#10
REVIEW
Marina Burgos da Silva, Flavia Franco da Cunha, Fernanda Fernandes Terra, Niels Olsen Saraiva Camara
The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection...
February 24, 2017: World Journal of Transplantation
https://www.readbyqxmd.com/read/28277274/therapeutic-reversal-of-food-allergen-sensitivity-by-mature-retinoic-acid-differentiated-dendritic-cell-induction-of-lag3-cd49b-foxp3-regulatory-t%C3%A2-cells
#11
Wojciech Dawicki, Chunyan Li, Jennifer Town, Xiaobei Zhang, John R Gordon
BACKGROUND: Anaphylaxis is a life-threatening condition for which we have limited therapeutic options. Although specific immunotherapy for food allergies is becoming more effective, it is still laborious and carries substantial risk of adverse events. On the other hand, regulatory dendritic cell (DC) therapy is effective in mouse models of allergic disease and has been shown to work with TH2 cells from atopic asthmatic patients. OBJECTIVE: We assessed whether DC immunotherapy could reverse food allergen sensitivity in mouse models to provide proof of concept relating to their use in the clinic...
October 20, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28271982/hepatic-mir-301a-as-a-liver-transplant-rejection-biomarker-and-its-role-for-interleukin-6-production-in-hepatocytes
#12
Toshiaki Nakano, I-Hsuan Chen, Shigeru Goto, Chia-Yun Lai, Hui-Peng Tseng, Li-Wen Hsu, King-Wah Chiu, Chih-Che Lin, Chih-Chi Wang, Yu-Fan Cheng, Chao-Long Chen
Acute rejection (AR) of liver transplantation remains a formidable challenge for diagnostic medicine and biomarker discovery. We characterized AR-related microRNAs (miRNAs) and the underlying AR mechanisms in liver transplantation. Using a rat model of orthotopic liver transplantation (OLT) as well as microarrays, we compared the miRNA expression profiles between naive and AR livers on day 7 after OLT with short- (<14 days, donor Dark Agouti [DA] liver into Lewis [LEW] recipient) and long-term (>60 days, donor DA liver into Piebald Virol Glaxo [PVG] recipient) survival fates...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28262752/highly-exposed-hiv-1-seronegative-female-commercial-sex-workers-sustain-in-their-genital-mucosa-increased-frequencies-of-tolerogenic-myeloid-and-regulatory-t-cells
#13
V Thibodeau, L Fourcade, A-C Labbé, M Alary, F Guédou, J Poudrier, M Roger
We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-α, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-α, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261223/regulatory-b-cells-in-pregnancy-lessons-from-autoimmunity-graft-tolerance-and-cancer
#14
REVIEW
Ruth Marian Guzman-Genuino, Kerrilyn R Diener
The success of pregnancy is contingent on the maternal immune system recognizing and accommodating a growing semi-allogeneic fetus. Specialized subsets of lymphocytes capable of negative regulation are fundamental in this process, and include the regulatory T cells (Tregs) and potentially, regulatory B cells (Bregs). Most of our current understanding of the immune regulatory role of Bregs comes from studies in the fields of autoimmunity, transplantation tolerance, and cancer biology. Bregs control autoimmune diseases and can elicit graft tolerance by inhibiting the differentiation of effector T cells and dendritic cells (DCs), and activating Tregs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28260519/immune-tolerance-of-mesenchymal-stem-cells-and-induction-of-skin-allograft-tolerance
#15
Tengxiao Ma, Xiao Wang, Duyin Jiang
Mesenchymal stem cells not only possess reparative properties, but also have immunomodulatory effect. Owing to the properties, they have been proposed to be hopeful candidates for cell therapy in the process of organ transplantation. In the preclinical researches, it shows that MSCs is capable of prolonging graft survival and inducing tolerance in some cases. Various mechanisms of immune tolerance were reported before, such as tolerogenic dendritic cells, induction of apoptosis, regulatory T cells, mixed chimerism, soluble factors and anergy...
March 1, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28256612/the-role-of-indoleamine-2-3-dioxygenase-aryl-hydrocarbon-receptor-pathway-in-the-tlr4-induced-tolerogenic-phenotype-in-human-dcs
#16
Fabián Salazar, Dennis Awuah, Ola H Negm, Farouk Shakib, Amir M Ghaemmaghami
A controlled inflammatory response is required for protection against infection, but persistent inflammation causes tissue damage. Dendritic cells (DCs) have a unique capacity to promote both inflammatory and anti-inflammatory processes. One key mechanism involved in DC-mediated immunosuppression is the expression of tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO). IDO has been implicated in diverse processes in health and disease but its role in endotoxin tolerance in human DCs is still controversial...
March 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28254840/extracellular-matrix-and-the-myeloid-in-myeloma-compartment-balancing-tolerogenic-and-immunogenic-inflammation-in-the-myeloma-niche
#17
REVIEW
Fotis Asimakopoulos, Chelsea Hope, Michael G Johnson, Adam Pagenkopf, Kimberly Gromek, Bradley Nagel
The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomide analogs) and proteasome inhibitors that target crucial pathways that regulate immunity and inflammation, such as NF-κB. This paradigm continued with the recent regulatory approval of mAbs (elotuzumab, daratumumab) that impact both tumor cells and associated immune cells...
March 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28239436/gut-microbiota-in-a-rat-oral-sensitization-model-effect-of-a-cocoa-enriched-diet
#18
Mariona Camps-Bossacoma, Francisco J Pérez-Cano, Àngels Franch, Margarida Castell
Increasing evidence is emerging suggesting a relation between dietary compounds, microbiota, and the susceptibility to allergic diseases, particularly food allergy. Cocoa, a source of antioxidant polyphenols, has shown effects on gut microbiota and the ability to promote tolerance in an oral sensitization model. Taking these facts into consideration, the aim of the present study was to establish the influence of an oral sensitization model, both alone and together with a cocoa-enriched diet, on gut microbiota...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28231415/encapsulating-an-immunosuppressant-enhances-tolerance-induction-by-siglec-engaging-tolerogenic-liposomes
#19
Lijuan Pang, Matthew S Macauley, Britni M Arlian, Corwin M Nycholat, James C Paulson
Unwanted antibody responses significantly impact human health, and current options for treating deleterious antibody responses largely rely on broad immunosuppressants that can compromise overall immunity. A desirable alternative is to induce antigen-specific immune tolerance. We have shown that co-presentation of antigen and ligands of B cell Siglecs (sialic acid-binding immunoglobulin-like lectin) on a liposomal nanoparticle induces antigen-specific tolerance. Although Siglec-engaging tolerance-inducing antigenic liposomes (STALs) induce robust B cell tolerance in naïve mice, the full potential of STALs requires long-term tolerance induction and suppression of an ongoing immune response...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28230210/synergistic-suppression-of-autoimmune-arthritis-through-concurrent-treatment-with-tolerogenic-dc-and-msc
#20
Rong Li, Yujuan Zhang, Xiufen Zheng, Shanshan Peng, Keng Yuan, Xusheng Zhang, Weiping Min
Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive immune-mediated joint deterioration. Current treatments are not antigen specific and are associated with various adverse. We have previously demonstrated that tolerogenic dendritic cells (Tol-DC) are potent antigen-specific immune regulators, which hold great promise in immunotherapy of autoimmune diseases. In this study, we aimed to develop new immunotherapy by combining Tol-DC and mesenchymal stem cells (MSC). We demonstrated that RelB gene silencing resulted in generation of Tol-DC that suppressed T cell responses and selectively promoted Treg generation...
February 23, 2017: Scientific Reports
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