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Monovalent mannose-glycoconjugates of sulforaphane reprogram human dendritic cells via NFATc1 to induce immune tolerance under inflammatory conditions.

BACKGROUND AND PURPOSE: Immune tolerance prevents inflammation and autoimmunity, with dendritic cells (DCs) playing a key role. Reprogramming DCs towards a tolerogenic state represents a promising therapeutic strategy. Sulforaphane (SFN) has known immunomodulatory effects, but its clinical application is limited by poor stability and bioavailability. To enhance its therapeutic potential, SFN was conjugated with mannose (SFNMan) or fucose (SFNFuc), aiming to induce a tolerogenic phenotype in human monocyte-derived DCs (moDCs) under inflammation and to explore NFATc1's involvement. EXPERIMENTAL…

АнтиPD-L1-IFN-α-обезвреженная вакцина против ГБсага помогает преодолеть иммунную терпимость к ГБВ, реанимируя как РС, так и макрофаги.

Вакцина против эпидемического гепатита В (ROHBsAg) с различными адвуантами не нарушает допуски по Т и В клеткам в приемных домах с хроническим гепатитом В (CHB). Цель этого исследования заключается в изучении механизмов, позволяющих нарушить иммунную терпимость, позволяющую носителю реагировать на RHBAg, и найти лекарство от CHB. Мы создали анти-PD-L1-IFN-α (APD-L1-IFN-α) гетеродимерный белок синтеза, который позволяет RHBSAg омолаживать реакцию клеток Т и В в мышах, подверженных вирусу В (HBV-терпимости). S.c. communization with aPD-L1-IFN-α и rHBSAg значительно усилили поглощение и созревани

Совпадение в аннотации оригинала
Recombinant hepatitis B surface antigen (rHBsAg) vaccine with various adjuvants fails to break T and B cell tolerance in hosts with chronic hepatitis B (CHB). This study aims to explore the mechanisms to break immune tolerance that allows the host to respond to rHBsAg, achieving a cure for CHB. We engineered an anti-PD-L1-IFN-α (aPD-L1-IFN-α) heterodimeric f…

Mesoporous polydopamine nanoparticle-based tolerogenic vaccine induces antigen-specific immune tolerance to prevent and treat autoimmune multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disorder derived from autoreactive immune system attacking the protective myelin sheath that surrounds nerves in the central nervous system (CNS). Here, a tolerogenic nanovaccine for generating an antigen-specific immune tolerance for treating MS is proposed. It consisted of a mesoporous polydopamine (mPDA) nanoparticle, characterized by high reactive oxygen species (ROS)-scavenging property, loaded with MS-derived autoantigen. Intravenous vaccination of autoantigen-loaded mPDA could induce tolerogenic dendritic cells (DCs) with low expression …

The role of tryptophan metabolism and tolerogenic dendritic cells in maintaining immune tolerance: Insights into celiac disease pathogenesis.

BACKGROUND: In mammals, amino acid metabolism has evolved to control immune responses. Tryptophan (Trp) is the rarest essential amino acid f … contribute to the pathogenesis of CeD. Tolerogenic DCs, in particular, are instrumental in inducing immune tolerance, leading to T-reg differentiation that helps maintain intestinal immune tolerance against inflammatory responses in CeD patients and those with other autoimmune disorders. T-regs, a subset of T-cells, play a crucial role in maintaining intestinal im …

Achieving symptom relief in patients with myalgic encephalomyelitis by targeting the neuro-immune interface and optimizing disease tolerance.

Myalgic encephalomyelitis (ME) previously also known as chronic fatigue syndrome is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem oft

First successful concomitant therapy of immune tolerance induction therapy and desensitization in a CRIM-negative infantile Pompe patient.

OBJECTIVES: Enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA) has changed the fatal course of infantile Pompe disease, however, development of anti rhGAA antibodies and infusion-associated reactions (IAR) restrict the tolerability and effectiveness of the treatment. CASE PRESENTATION: We describe a successful concomitant immune tolerance induction (ITI) and desensitization protocols in a cross-reactive immunologic material (CRIM) negative 7-month-old male patient. At the age of 5 months and eighth dose of the ERT, the patient developed IAR and his rhGAA specific IgE was negativ…

Immune tolerance of allogeneic haematopoietic cell transplantation supports donor epidermal grafting of recessive dystrophic epidermolysis bullosa chronic wounds.

BACKGROUND: Chronic wounds, a common morbidity in recessive dystrophic epidermolysis bullosa (RDEB), lack definitive therapies. OBJECTIVES: … ive skin). This strategy subsequently supported release of RDEB pseudosyndactyly. CONCLUSIONS: The immune tolerance established by alloHCT supports successful adoptive transfer of donor epidermal grafts. Persistence of donor grafts in a single patient beyond 1 year and observed migration of donor-grafted cells into adjacent wound suggest that epidermal allografts …

Impact of CMV Reactivation, Treatment Approaches, and Immune Reconstitution in a Nonmyeloablative Tolerance Induction Protocol in Cynomolgus Macaques.

BACKGROUND: Cytomegalovirus (CMV) infection is a serious complication in immunosuppressed patients, specifically transplant recipients. Here, we describe the development and use of an assay to monitor the incidence and treatment of CMV viremia in a Cynomolgus macaque model of bone marrow transplantation (BMT) for tolerance induction. We address the correlation between the course of viremia and immune reconstitution. METHODS: Twenty-one animals received a nonmyeloablative conditioning regimen. Seven received cyclosporine A for 28 days and 14 received rapamycin. A CMV polymerase chain reaction

Immune tolerance attenuates gut dysbiosis, dysregulated uterine gene expression and high-fat diet potentiated preterm birth in mice.

BACKGROUND: Preterm delivery accounts for 85% of perinatal morbidity and mortality. Although the consumption of a high-fat diet leads to exa … immune response on the microbiome, transcriptome, and risk of spontaneous preterm birth, we induced immune tolerance with repetitive subclinical doses (0.2 mg/kg/week for 8 weeks) of endotoxin and performed 16S ribosomal RNA and uterine transcriptome sequencing on these immunotolerized mice. RESULTS: High-fat diet potentiates lipopolysaccharide-induced preterm bi …

Rat strain differences in peritoneal immune cell response to selected gut microbiota: A crossroad between tolerance and autoimmunity?

AIMS: Some gut commensals can be protective, whereas others are implicated as necessary for development of inflammatory/autoimmune diseases. Peritoneal immune cells may play an important role in promoting autoimmunity in response to gut microbiota. This study investigated the phenotype and the function of peritoneal immune cells in the autoimmunity-resistant Albino Oxford (AO), and the autoimmunity-prone Dark Agouti (DA) rat strains upon stimulation with their own colonic E. coli or Enterococcus. MAIN METHODS: Rats were intraperitoneally injected with their own E. coli or Enterococcus. Perito

Role of regulatory T cells in CD47/donor-specific transfusion-induced immune tolerance in skin-heart transplantation mice.

OBJECTIVES: To explore the role of regulatory T (Treg ) cells in the establishment of immune tolerance induced by donor-specific transfusion (DST) in mice with skin-heart transplantation. METHODS: C57BL/6 mice received DST of splenocytes from CD47+/+ or CD47-/- H-2bm1 mice or no DST 7 days before skin-heart transplantation from major histocompatibility complex class I-mismatched H-2bm1 donors. The number and proportion of Treg cells in graft and lymphoid organs were measured by flow cytometry (FACS) and immunohistochemistry (IHC). The inhibitory function of Treg cells and anti-donor T-cell re…

Effect of miR-30e regulating NK cell activities on immune tolerance of maternal-fetal interface by targeting PRF1.

AIM: Natural killer (NK) cells, as key regulatory cells, accumulate at the maternal-fetal interface in large numbers. This study explored the effect of miR-30e on regulating the activity and function of peripheral blood NK cells (PB-NK cells) and decidua NK cells (D-NK cells) by targeting PRF1 in immune tolerance of maternal-fetal interface. METHODS: Expressions of miR-30e in PB and decidua tissues from 49 patients with recurrent spontaneous abortion and 52 normal pregnant women were measured using PCR. NK cells were isolated from PB and decidua tissues and identified by flow cytometry (FCM).…

Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy.

OBJECTIVES: IL-35 is a novel inhibitory cytokine. In this study, we investigate the serum levels of inhibitory cytokines IL-35, IL-10 and TGF-β in both normal pregnancies and non-pregnant females, and whether IL-35 is associated with the pathogenesis of recurrent spontaneous abortion. We also try to elucidate the relationships of IL-35 with estrogen and alpha-fetoprotein (AFP). METHODS: The levels of IL-35, IL-10, TGF-β, estradiol (E2), unconjugated estriol (uE3) and AFP were analyzed in 120 normal pregnancies, 40 women suffering recurrent spontaneous abortion, 40 postpartum healthy women and

Decidual vascular endothelial cells promote maternal-fetal immune tolerance by inducing regulatory T cells through canonical Notch1 signaling.

Adaptation of the maternal immune response to accommodate the semiallogeneic fetus is necessary for pregnancy success. However, the mechanisms by which the fetus avoids rejection despite expression of paternal alloantigens remain incompletely understood. Regulatory T cells (Treg cells) are pivotal for maintaining immune homeostasis, preventing autoimmune disease and fetus rejection. In this study, we found that maternal decidual vascular endothelial cells (DVECs) sustained Foxp3 expression in resting Treg cells in vitro. Moreover, under in vitro Treg cell induction condition with agonistic ant

Plant-based oral tolerance to hemophilia therapy employs a complex immune regulatory response including LAP+CD4+ T cells.

Coagulation factor replacement therapy for the X-linked bleeding disorder hemophilia is severely complicated by antibody ("inhibitor") formation. We previously found that oral delivery to hemophilic mice of cholera toxin B subunit-coagulation factor fusion proteins expressed in chloroplasts of transgenic plants suppressed inhibitor formation directed against factors VIII and IX and anaphylaxis against factor IX (FIX). This observation and the relatively high concentration of antigen in the chloroplasts prompted us to evaluate the underlying tolerance mechanisms. The combination of oral deliver

Maintenance of immune tolerance to a neo-self acetylcholine receptor antigen with aging: implications for late-onset autoimmunity.

Age-related changes in immune regulation are likely to account for the age-associated increase in serum autoantibody levels and in certain autoimmune disorders, such as myasthenia gravis (MG). To demonstrate directly a loss of immune tolerance in older individuals, responses to the acetylcholine receptor, the autoantigen in MG, were assessed in transgenic mice expressing the Torpedo californica acetylcholine receptor (TAChR) alpha-chain as a neo-self Ag. T cells from young transgenic mice had been shown to be tolerant to p146-162, the TAChR alpha-chain peptide that dominated young nontransgeni…

Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome: a preliminary study.

BACKGROUND: Post-streptococcal autoimmune inflammation of basal ganglia was suggested to be an etiological factor in some cases of Tourette syndrome (TS). Since regulatory T (T reg) cells play a major role in preventing autoimmunity, we hypothesized that a defect in T reg cells may be present in children with TS. We also postulated that group A beta hemolytic streptococcal infections could promote autoimmune responses by releasing exotoxins (streptococcal pyrogenic exotoxins [SPE]). METHODS: We analyzed peripheral blood of TS patients and healthy age-matched control subjects by fluorescence-a

Cutting edge: persistent viral infection prevents tolerance induction and escapes immune control following CD28/CD40 blockade-based regimen.

A continuing concern with CD28 and/or CD40 blockade-based strategies to induce tolerance and mixed chimerism is their potential to disrupt protective immunity to preexisting infections. In this report, we find that preexisting persistent infection with lymphocytic choriomeningitis virus (LCMV) clone 13 prevents the induction of tolerance, mixed chimerism, and donor-reactive T cell deletion. Mice continue to be refractory to tolerance induction even after viremia has been resolved and virus is present only at very low levels in peripheral tissues. Conversely, we find that the full tolerance reg

On the Similarity Between Postpartum Autoimmune Abnormalities and Immune-Related Adverse Events (irAE) by Immune Checkpoint Inhibitors (ICI): The Placenta as a PD-L1-Rich Immune-Tolerant Organ.

Immune tolerance is essential for safeguarding the body's own tissues from immune system attacks. During pregnancy, the maternal immune system tolerates the semi-allogeneic fetus through mechanisms such as placental programmed cell death 1 (PD-1)-ligand 1 (PD-L1) expression, regulatory T cells (Tregs), cytokine modulation, and hormonal changes. Placental PD-L1 is particularly important in suppressing maternal immune responses and preventing fetal rejection. Following delivery, the loss of the PD-L1-rich placenta can destabilize immune tolerance, potentially leading to postpartum autoimmune dis…

The role of the bursa of Fabricius in the immune response to vaccinal antigens and the development of immune tolerance in chicks (Gallus domesticus) vaccinated at a very young age.

Vaccination is recognized to be the most cost-effective means of preventing, controlling, and even eradicating infectious diseases. Conventional poultry are vaccinated through various routes including eye/nose drops, drinking water, vent brush, or injection. Efficient vaccination is an essential part of any good poultry management.The bursa of Fabricius is intimately connected to the cloaca and the intestinal system. It is well-known as a primary lymphoid organ in the chicken and a major channel through which environmental antigens stimulate the immune system. In this study we tested whether d