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Systemic TLR2 tolerance enhances central nervous system remyelination.

BACKGROUND: Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease characterized by both inflammatory demyelination and impaired remyelination. Studies indicate that Toll-like receptor 2 (TLR2) signaling contributes to both the inflammatory component and the defective remyelination in MS. While most MS therapeutics target adaptive immunity, we recently reported that reducing TLR2 signaling in innate immune cells by inducing TLR2 tolerance attenuates adoptively transferred experimental autoimmune encephalomyelitis. Given that previous reports suggest TLR2 signaling also in

Hematopoietic stem cell transplantation improves the high incidence of neutralizing allo-antibodies observed in Hurler's syndrome after pharmacological enzyme replacement therapy.

BACKGROUND: Mucopolysaccharidosis type I is caused by deficiency of α-L-iduronidase. Currently available treatment options include an alloge … previously received an allogeneic stem cell transplant were tested to evaluate this treatment as an immune tolerance induction mechanism. RESULTS: High titer immune responses were seen in 87.5% (7/8) patients following exposure to α-L-iduronidase. These patients exhibited catalytic enzyme inhibition (5/8), uptake inhibition of catalytically active enzyme (6/8) or …

B Cell Responses to the Placenta and Fetus.

Pregnancy has fascinated immunologists ever since Peter Medawar's observation that reproduction runs contrary to the founding tenets of immunology. During healthy pregnancy, maternal B cells interact with antigens of the foreign conceptus (placenta and fetus) yet do not elicit rejection. Instead, robust and redundant fetomaternal tolerance pathways generally prevent maternal B cells and antibodies from harming the placenta and fetus. Fetomaternal tolerance is not absolute, and unfortunately there exist several pregnancy complications that arise from breaks therein. Here, important historic and

Determinants of Epitope Immunodominance Hierarchies in Protein Antigens at the Molecular, Structural, and Cellular Levels, Including MHC-Dependent Mechanisms.

BACKGROUND: Epitope immunodominance describes the phenomenon whereby some antigenic epitopes preferentially elicit immune responses, whereas other epitopes remain subdominant or immunologically silent. Epitope immunodominance hierarchies are the result of coordinated molecular, structural, and cellular mechanisms. These hierarchies emerge from selective immune recognition processes that balance effective immunity and self-tolerance mechanisms. OBJECTIVE: The aim of this study is to describe the molecular, structural, and cellular parameters that mediate epitope immunodominance in antigens. In

Витамин D как модулятор иммуно-эндокрина: открытие его роли в аутоиммунных расстройствах и механизмах защиты заложников.

Фон/цели: Витамин D, получивший всеобщее признание за свою роль в гомеостазе кальция-фосфата и здоровье скелета, стал одним из ключевых модуляторов иммуноэндокринной системы. Его активный метаболит взаимодействует с рецептором витамина D (VDR) через иммунную и эндокринную клетку, оказывая влияние на транскрипцию генов, баланс цитокина и иммунную терпимость. В настоящем докладе обобщаются механистические, эпидемиологические и клинические данные о роли витамина D в иммунной модуляции различных аутоиммунных и инфекционных заболеваний. Методы: Этот описательный обзор включал структурированный и вс

Совпадение в аннотации оригинала
Background/Objectives: Vitamin D, universally recognized for its role in calcium-phosphate homeostasis and skeletal health, has emerged as a key immuno-endocrine modulator. Its active metabolite interacts with the vitamin D receptor (VDR) across immune and endocrine cell populations, influencing gene transcription, cytokine balance, and immune tolerance. Thi…

[Gut microbiota and allergic diseases].

Incidence of allergic diseases continues to increase, particularly among children, and has become an important public health concern. As a key link connecting environmental exposure, immune development, and susceptibility to allergic diseases, the gut microbiota has emerged as an important focus of related research. The gut microbiota plays a crucial role in immune system maturation during early life, establishment of immune tolerance, and maintenance of mucosal barrier integrity. Gut dysbiosis may contribute to the occurrence and progression of allergic diseases through multiple mechanisms, i…

A HO-1 gene knockout using a NanoCRISPR scaffold suppresses metastasis in mouse models.

Photodynamic therapy-induced immunogenic cell death has the potential to generate autologous cancer vaccines. However, the innate or evolved genetic tolerance of tumours limits the efficacy of this approach. Here we report the development of a heritable nanoplatform based on gene editing of haem oxygenase-1 (HO-1) using a NanoCRISPR/HO-1 scaffold. This platform effectively eliminates genetic tolerance to reactive oxygen species in tumours without causing adverse effects on main immune cells, resulting in a robust and durable immune response to autologous vaccine. This NanoCRISPR scaffold can i

Immunotherapy and the Combination with Targeted Therapies for Advanced Hepatocellular Carcinoma.

One of the most important abilities of a tumor is to establish a state of immunosuppression inside the tumor microenvironment. This is made possible through numerous mechanisms of tumor immune escape that have been identified in experimental studies during the last decades. In addition, the hepatic microenvironment is commonly oriented towards a state of immune tolerance because the liver receives blood from the hepatic arteries and portal veins containing a variety of endogenous antigens. Therefore, the hepatic microenvironment establishes an autoimmune tolerance, preventing an autoimmune rea…

T Lymphocytes and Testicular Immunity: A New Insight into Immune Regulation in Testes.

The immune privilege of the testes is necessary to prevent immune attacks to gamete-specific antigens and paternal major histocompatibility complex (MHC) antigens, allowing for normal spermatogenesis. However, infection and inflammation of the male genital tract can break the immune tolerance and represent a significant cause of male infertility. Different T cell subsets have been identified in mammalian testes, which may be involved in the maintenance of immune tolerance and pathogenic immune responses in testicular infection and inflammation. We reviewed the evidence in the published literat…

A Unique Perspective on Auto-reactive Antibody Production in Autoimmune Disease Induced by Microbiome.

Activation of autoreactive lymphocytes leads to cellular and tissue damage, which results in the development of autoimmune diseases. External environmental changes, such as chronic microbial infections, can alter the immune homeostasis and disrupt the balance of autoreactive T and B cells. In this review, we first summarize immune tolerance mechanisms of T and B cells, and then describe the breakthroughs of immune tolerance in T and B cells, followed by related autoimmune diseases. Furthermore, we explore how microbial infections can induce the production of autoreactive antibodies via carrier…

Taming autoimmune thyroiditis: cellular immunomodulation through MSCs, Tregs, and tolDCs.

Autoimmune thyroiditis (AIT), typified by Hashimoto's thyroiditis, represents a prototypical organ-specific autoimmune disorder marked by ly … notherapeutic strategy to modify AIT progression, moving beyond symptomatic relief toward long-term immune tolerance.

Intragraft gene expression profile associated with the induction of tolerance.

BACKGROUND: Xenotransplantation holds the promise of providing an unlimited supply of donor organs for terminal patients with organ failure. Pre-existing natural antibodies to the Galalpha1,3Galbeta1,4GlcNac-R (alphaGal) carbohydrate xenoantigen, however, bind rapidly to the graft endothelium and initiate hyperacute rejection of wild type pig grafts in humans. Experimental procedures designed to prevent xenoantibody-mediated rejection have been tested in gal knockout mice. These mice produce anti-gal xenoantibodies and are widely used as small animal models for xenotransplantation research. In

Extracellular vesicle signaling in regulatory T cell biology: From immune suppression to microenvironmental crosstalk.

Regulatory T cells (Tregs) are essential for maintaining immune homeostasis, yet classical suppressive mechanisms alone do not fully explain … ion, infection and cancer, this bidirectional crosstalk emerges as a context-dependent regulator of immune tolerance that may either preserve tissue homeostasis or promote pathological immune suppression. We finally consider the therapeutic potential of targeting or engineering EV-Treg interactions as a cell-free strategy for precision immunomodulation.

The dual role of IgG4 in immunity: bridging pathophysiology and therapeutic applications.

IgG4 antibodies exhibit unique structural and functional properties, which distinguish them from other IgG subclasses. Among clinicians, IgG4 has been primarily associated with IgG4-related diseases (IgG4-RDs), such as autoimmune pancreatitis, where its role has been a focus of intense discussion. However, growing evidence reveals that IgG4 is involved in a broader spectrum of immune-regulatory processes, extending beyond IgG4-RDs and positioning it as a key modulator of immune tolerance. In this context, several specific features allow IgG4 to play dual roles, serving as a protective factor i…

Genetic and Iatrogenic Defects in Peripheral Tolerance Associated with Anti-Nephrin Antibody-Associated Minimal Change Disease.

INTRODUCTION: Minimal change disease (MCD) is a common cause of nephrotic syndrome in children and adults. Immune dysregulation is a contributor, but the relative roles of individual components of the immune system in MCD pathogenesis remain unclear. CASE PRESENTATION: Here, we present 2 patients with defects in immune tolerance mechanisms that developed MCD associated with anti-nephrin antibodies. The first patient had a pathogenic deletion in FOXP3, leading to reduced regulatory T cells. Serum could not be obtained from this patient during the active phase of MCD to directly establish the p…

Glut3 promotes cellular O-GlcNAcylation as a distinctive tumor-supportive feature in Treg cells.

Regulatory T cells (Tregs) establish dominant immune tolerance but obstruct tumor immune surveillance, warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs (TIL-Tregs). We show that enhanced posttranslational O-linked N-acetylglucosamine modification (O-GlcNAcylation) of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts. We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process. Treg-s…

Altered frequency and function of spleen CTLA-4+Tim-3+ T cells are associated with miscarriage†.

Normal pregnancy is associated with several immune adaptations in both systemic and local maternal-fetal interface to allow the growth of semi-allogeneic conceptus. A failure in maternal immune tolerance to the fetus may result in abnormal pregnancies, such as recurrent spontaneous abortion. The regulation of T-cell homeostasis during pregnancy has important implications for maternal tolerance and immunity. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and T-cell immunoglobulin mucin-3 (Tim-3) are important negative immune regulatory molecules involved in viral persistence and tumor metastasis. He…

Hepatic immune regulation and its involvement in viral hepatitis infection.

The liver has unique immune regulatory functions that promote the induction of tolerance rather than responses to antigens encountered locally. These functions are mediated by local expression of coinhibitory receptors and immunosuppressive mediators that help prevent overwhelming tissue damage. Over the years, we have gained more insight into the local regulatory cues that determine the functional complexity of immune responses regulated locally in the liver. Both the unique hepatic microenvironment and the particular liver sinusoidal cell populations, in addition to hepatocytes, actively mod

Imiquimod-induced dermatitis impairs thymic tolerance of autoreactive CD4+ T cells to desmoglein 3.

BACKGROUND: The thymus plays an essential role in removing autoreactive T cells. Autoantigen-expressing thymic epithelial cells (TECs) contribute to the tolerogenic process. The thymus transiently shrinks as an acute thymic involution (ATI) under various inflammatory conditions. However, whether ATI occurs during local skin inflammation remains unclear, as does its influence on thymic immune tolerance. OBJECTIVE: We investigated whether imiquimod-induced dermatitis causes ATI and impairs thymic immune tolerance against desmoglein 3 (Dsg3), an epidermal autoantigen of pemphigus vulgaris. METH…

Mucosal immunity in cancer metastasis: roles, mechanisms, and therapeutic implications.

Previous studies have shown that the mucosal immune system plays a crucial role in regulating immune tolerance, maintaining the integrity of the mucosal barrier, and facilitating immune communication between organs. However, its role in tumor metastasis has not been fully investigated. This review integrates recent studies on mucosal immunity and tumor metastasis, systematically discussing the process by which mucosal immune dysregulation promotes tumor metastasis. We elucidate how the mucosal imprinting program formed within the common mucosal immune system affects metastasis through regulati…