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https://www.readbyqxmd.com/read/28231415/encapsulating-an-immunosuppressant-enhances-tolerance-induction-by-siglec-engaging-tolerogenic-liposomes
#1
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
#2
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
https://www.readbyqxmd.com/read/28229217/foxo3-estrogen-receptor-alpha-and-androgen-receptor-impact-tumor-growth-rate-and-infiltration-of-dendritic-cell-subsets-differentially-between-male-and-female-mice
#3
Matthew G Thompson, Daniel S Peiffer, Michelle Larson, Flor Navarro, Stephanie K Watkins
Tumors evade immune recognition and destruction in many ways including the creation of an immune-suppressive tumor microenvironment (TME). Dendritic cells (DC) that infiltrate the TME are tolerogenic, and suppress effector T cells and anti-tumor activity. Previous reports demonstrated that a key regulator of tolerance in DC is the transcription factor FOXO3. Gender disparity has been studied in cancer in relation to incidence, aggressiveness, and prognosis. Few studies have touched on the importance in relation to impact on the immune system...
February 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#4
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28222739/generation-of-donor-specific-tr1-cells-to-be-used-after-kidney-transplantation-and-definition-of-the-timing-of-their-in-vivo-infusion-in-the-presence-of-immunosuppression
#5
Bechara Mfarrej, Eleonora Tresoldi, Angela Stabilini, Alessia Paganelli, Rossana Caldara, Antonio Secchi, Manuela Battaglia
BACKGROUND: Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell-based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell-based therapy after kidney transplantation. METHODS: Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell-enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28218625/egress-of-sperm-autoantigen-from-seminiferous-tubules-maintains-systemic-tolerance
#6
Kenneth S K Tung, Jessica Harakal, Hui Qiao, Claudia Rival, Jonathan C H Li, Alberta G A Paul, Karen Wheeler, Patcharin Pramoonjago, Constance M Grafer, Wei Sun, Robert D Sampson, Elissa W P Wong, Prabhakara P Reddi, Umesh S Deshmukh, Daniel M Hardy, Huanghui Tang, C Yan Cheng, Erwin Goldberg
Autoimmune responses to meiotic germ cell antigens (MGCA) that are expressed on sperm and testis occur in human infertility and after vasectomy. Many MGCA are also expressed as cancer/testis antigens (CTA) in human cancers, but the tolerance status of MGCA has not been investigated. MGCA are considered to be uniformly immunogenic and nontolerogenic, and the prevailing view posits that MGCA are sequestered behind the Sertoli cell barrier in seminiferous tubules. Here, we have shown that only some murine MGCA are sequestered...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28216098/potential-influences-of-complement-factor-h-in-autoimmune-inflammatory-and-thrombotic-disorders
#7
Janez Ferluga, Lubna Kouser, Valarmathy Murugaiah, Robert B Sim, Uday Kishore
Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part...
February 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28215928/human-platelet-lysate-is-a-successful-alternative-serum-supplement-for-propagation-of-monocyte-derived-dendritic-cells
#8
Urban Švajger
BACKGROUND AIMS: Clinical protocols for dendritic cell (DC) generation from monocytes require the use of animal serum-free supplements. Serum-free media can also require up to 1% of serum supplementation. In addition, recommendations based on the 3Rs (Refinement, Reduction, Replacement) principle also recommend the use of non-animal sera in in vitro studies. The aim of this study was to explore the potential use of platelet lysate (PL) for generation of optimally differentiated DCs from monocytes...
February 16, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28214929/myeloid-cells-as-a-target-for-oligonucleotide-therapeutics-turning-obstacles-into-opportunities
#9
REVIEW
Marcin Kortylewski, Dayson Moreira
Immunotherapies emerged as an alternative for cancer treatment, yet their clinical efficacies are still limited, especially in case of solid tumors. Myeloid immune cells, such as macrophages and myeloid-derived suppressor cells (MDSCs), are often hijacked by tumors and become pivotal inhibitors of antitumor immunity. Immunosuppressive functions of tumor-associated myeloid cells result from the activity of Signal Transducer and Activator of Transcription 3 (STAT3), a transcription factor with well-defined tumorigenic and tolerogenic roles in human cancers...
February 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28209270/crosstalk-between-glucocorticoids-and-il-4-modulates-ym1-expression-in-alternatively-activated-myeloid-cells
#10
Nathalie Ng Kuet Leong, Frank Brombacher, Alexander H Dalpke, Michael Weitnauer
Airway epithelial cells induce a tolerogenic microenvironment by modulating immune cells in the lung. We recently showed that the supernatant of airway epithelial cells induces two marker genes of alternative activation, Ym1 and Ms4a8a, in respiratory myeloid cells. This induction was partially mediated by glucocorticoids, secreted by airway epithelial cells. In this study, we further investigated Ym1 and Ms4a8a regulation in alternatively activated myeloid cells in the presence of the TH2 cytokines IL-4 and IL-13...
February 9, 2017: Immunobiology
https://www.readbyqxmd.com/read/28205558/plant-based-vaccines-for-oral-delivery-of-type-1-diabetes-related-autoantigens-evaluating-oral-tolerance-mechanisms-and-disease-prevention-in-nod-mice
#11
Amanda L Posgai, Clive H Wasserfall, Kwang-Chul Kwon, Henry Daniell, Desmond A Schatz, Mark A Atkinson
Autoantigen-specific immunological tolerance represents a central objective for prevention of type 1 diabetes (T1D). Previous studies demonstrated mucosal antigen administration results in expansion of Foxp3(+) and LAP(+) regulatory T cells (Tregs), suggesting oral delivery of self-antigens might represent an effective means for modulating autoimmune disease. Early preclinical experiments using the non-obese diabetic (NOD) mouse model reported mucosal administration of T1D-related autoantigens [proinsulin or glutamic acid decarboxylase 65 (GAD)] delayed T1D onset, but published data are conflicting regarding dose, treatment duration, requirement for combinatorial agents, and extent of efficacy...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28201972/cell-based-tolerogenic-therapy-experience-from-animal-models-of-multiple-sclerosis-type-1-diabetes-and-rheumatoid-arthritis
#12
Ivana Stojanović, Mirjana Dimitrijević, Marta Vives-Pi, Maria Jose Mansilla, Irma Pujol-Autonell, Silvia Rodríguez-Fernandez, Lenka Palová-Jelínková, David P Funda, Alisa Gruden-Movsesijan, Ljiljana Sofronić-Milosavljević, Catharien M U Hilkens, Eva Martínez-Cáceres, Djordje Miljković
Cell-based tolerogenic therapy is a promising approach for the treatment of autoimmune diseases and transplant rejection. Regulatory T cells and tolerogenic dendritic cells have been particularly explored in the treatment of various autoimmune disorders in experimental models of disease. Although some of these cells have already been tested in a limited number of clinical trials, there is still a need for preclinical research on tolerogenic cells in animal models of autoimmunity. This review will focus on the relevance of data obtained from studies in experimental animal models for the use of tolerogenic cell-based therapy in humans...
14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#13
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193829/soluble-cd83-inhibits-t-cell-activation-by-binding-to-the-tlr4-md-2-complex-on-cd14-monocytes
#14
Joe M Horvatinovich, Elizabeth W Grogan, Marcus Norris, Alexander Steinkasserer, Henrique Lemos, Andrew L Mellor, Irina Y Tcherepanova, Charles A Nicolette, Mark A DeBenedette
The transmembrane protein CD83, expressed on APCs, B cells, and T cells, can be expressed as a soluble form generated by alternative splice variants and/or by shedding. Soluble CD83 (sCD83) was shown to be involved in negatively regulating the immune response. sCD83 inhibits T cell proliferation in vitro, supports allograft survival in vivo, prevents corneal transplant rejection, and attenuates the progression and severity of autoimmune diseases and experimental colitis. Although sCD83 binds to human PBMCs, the specific molecules that bind sCD83 have not been identified...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28186707/mesenchymal-stromal-cell-therapy-for-chronic-lung-allograft-dysfunction-results-of-a-first-in-man-study
#15
Daniel C Chambers, Debra Enever, Sharon Lawrence, Marian J Sturm, Richard Herrmann, Stephanie Yerkovich, Michael Musk, Peter M A Hopkins
Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD...
February 1, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28181012/oral-administration-of-the-lactic-acid-bacterium-pediococcus-acidilactici-attenuates-atherosclerosis-in-mice-by-inducing-tolerogenic-dendritic-cells
#16
Taiji Mizoguchi, Kazuyuki Kasahara, Tomoya Yamashita, Naoto Sasaki, Keiko Yodoi, Takuya Matsumoto, Takuo Emoto, Tomohiro Hayashi, Naoki Kitano, Naofumi Yoshida, Hilman Zulkifli Amin, Ken-Ichi Hirata
The intestinal microbiota appears to play an important role in the development of atherosclerosis. We investigated the effect of the probiotic lactic acid bacterium Pediococcus acidilactici R037 on atherosclerosis using apolipoprotein E-deficient (ApoE (-/-)) mice. Six-week-old ApoE (-/-) mice were orally administered R037 six times a week. Mice treated with R037 for 12 weeks exhibited markedly attenuated atherosclerotic lesions in the aortic root (2.3 ± 0.15 × 10(5) µm(2) vs. 3.3 ± 0.29 × 10(5) µm(2), respectively; P < 0...
February 8, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28174192/infarcted-myocardium-primed-dendritic-cells-improve-remodeling-and-cardiac-function-after-myocardial-infarction-by-modulating-the-treg-and-macrophage-polarization
#17
Eun Ho Choo, Jun-Ho Lee, Eun-Hye Park, Hyo Eun Park, Nam-Chul Jung, Tae-Hoon Kim, Yoon-Seok Koh, Eunmin Kim, Ki-Bae Seung, Cheongsoo Park, Kwan-Soo Hong, Kwonyoon Kang, Jie-Young Song, Han Geuk Seo, Dae-Seog Lim, Kiyuk Chang
BACKGROUND: -Inflammatory responses play a critical role in left ventricular (LV) remodeling after a myocardial infarction (MI). Tolerogenic dendritic cells (tDCs) can modulate immune responses inducing regulatory T cells (Tregs) in a number of inflammatory diseases. METHODS: -We generated tDCs by treating bone marrow-derived dendritic cells with TNF-α and cardiac lysate from MI mice. We injected MI mice, which were induced by a ligation of the left anterior descending coronary artery in C57BL/6 mice, twice with tDCs within 24 hours and at 7 days after the ligation...
February 7, 2017: Circulation
https://www.readbyqxmd.com/read/28173607/review-suggests-that-the-immunoregulatory-and-anti-inflammatory-properties-of-allergenic-foods-can-provoke-oral-tolerance-if-introduced-early-to-infants-diets
#18
REVIEW
Despina-Zoe T Mermiri, Theodora Lappa, Athina L Papadopoulou
: For years, the advice was to postpone introducing allergenic foods, in order to prevent food allergies. However, food allergies have escalated rather than declined and our review of the latest epidemiological, immunological and nutritional research suggests that early weaning practices may be beneficial. The most allergenic foods, such as fish, eggs and peanuts, have proved to be inherently rich in tolerogenic substances that can play a significant role in preventing allergies. CONCLUSION: We found evidence that the immunoregulatory and anti-inflammatory properties of allergenic foods can provoke oral tolerance if introduced early to both low-risk and high-risk infants...
February 7, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#19
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28166246/soluble-human-leukocyte-antigen-g-during-pregnancy-and-infancy-in-benin-mother-child-resemblance-and-association-with-the-risk-of-malaria-infection-and-low-birth-weight
#20
Tania C d'Almeida, Ibrahim Sadissou, Jacqueline Milet, Gilles Cottrell, Amandine Mondière, Euripide Avokpaho, Laure Gineau, Audrey Sabbagh, Achille Massougbodji, Kabirou Moutairou, Eduardo A Donadi, Benoit Favier, Edgardo Carosella, Philippe Moreau, Nathalie Rouas-Freiss, David Courtin, André Garcia
Human leukocyte antigen (HLA) G is a tolerogenic molecule involved in the maternal-fetal immune tolerance phenomenon. Its expression during some infectious diseases leading to immune evasion has been established. A first study conducted in Benin has shown that the production of soluble HLA-G (sHLA-G) during the first months of life is strongly correlated with the maternal level at delivery and associated with low birth weight and malaria. However sHLA-G measurements during pregnancy were not available for mothers and furthermore, to date the evolution of sHLA-G in pregnancy is not documented in African populations...
2017: PloS One
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