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Alterations of host resistance to Listeria monocytogenes in tumour-bearing mice and the effect of Corynebacterium parvum.

In tumour (fibrosarcoma)-inoculated mice, alterations of host resistance to Listeria monocytogenes following tumour growth were examined. Non-immune macrophage-mediated antibacterial resistance was severely suppressed up to day 4 or so after tumour inoculation, but was enhanced thereafter. On the other hand, T cell-mediated immune resistance retained the control level up to day 7 or so, but was suppressed thereafter. Suppression of macrophage-mediated antibacterial resistance was not observed if the tumour-bearing mice had been pretreated with Corynebacterium parvum. Moreover, this suppression

Miscarriage and the Microbiome: Host Genetics, Immunity, and the Reproductive Tract Ecosystem.

Background/Objectives: Pregnancy loss is a common and multifactorial complication of human reproduction, traditionally attributed to fetal chromosomal abnormalities, maternal anatomical and endocrine disorders, and immune dysfunction. Growing evidence now indicates that the maternal microbiome, particularly within the reproductive tract, plays a critical role in implantation, placental development, and the maintenance of immune tolerance during early pregnancy. Importantly, the influence of the microbiome on miscarriage appears to be strongly modulated by host genetic background and immune reg…

Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance.

The success of pregnancy relies on the fine adjustment of the maternal immune system to tolerate the allogeneic fetus. Trophoblasts carrying … less rapid or mature than that of cancer immunotherapy. Elucidating the mechanism of maternal-fetal immune tolerance, the theoretical basis for RSA immunotherapy, not only helps to understand the establishment and maintenance of normal pregnancy but also provides new therapeutic strategies and promotes the progress of immunotherapy against pregnancy-related diseas …

Kinetics of mast cell migration during transplantation tolerance.

BACKGROUND: After inflammatory stimulus, mast cells (MC) migrate to secondary lymphoid organs contributing to adaptive immune response. There is growing evidence that MC also contribute to transplant tolerance, but little is known about MC kinetics in the setting of transplant tolerance and rejection. Likewise it has been demonstrated that complement split products, which are known to act as chemoattractants for MC, are necessary for transplant tolerance. METHODS: Naive skin and lymph nodes, skin grafts and draining lymph nodes from wild type and complement deficient mice treated with a toler

Regulatory T cells in autoimmune diseases: biological mechanisms, clinical translation, and translational challenges.

Autoimmune diseases (ADs) are a group of inflammatory disorders triggered by aberrant immune responses against autoantigens and the breakdown of immune tolerance. Current therapeutic strategies, such as glucocorticoids and immunosuppressants, exert largely non-specific immunomodulation and are frequently associated with substantial adverse effects upon long-term administration. As such, these approaches are often insufficient to re-establish immune homeostasis. In recent years, regulatory T cell (Treg)-based therapeutics have undergone rapid advancement, with continuously updated therapeutic m…

Current state and future directions of basic research in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Despite advances in biologic therapies targeting inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, Janus kinase (JAK), and B cells, many patients do not respond adequately, emphasizing the need for deeper insights into RA pathogenesis. Research highlights the intricate interplay of genetic and epigenetic factors driving immune dysregulation. The breakdown of immune tolerance, often initiated in mucosal sites such as the gut, lung, and oral cavi…

Поврежденное выражение PTEN в Т ячейках приводит к сопротивлению мягким волнам в многоразовом склерозе.

Регулирование иммунной реакции с помощью клеток Т имеет важное значение для сохранения иммунной гомеостазии и профилактики аутоиммунных заболеваний. В множестве склерозов (MS) нарушение иммунорегулирования позволяет сохранять автоматически реактивные Т-элементы, поскольку эффектор Т-элементы (Teff) демонстрируют меньшую подверженность регуляционным Т-элементам (Treg). Это сопротивление допускам в отношении белковой киназы В (PKB/c-Akt) связано с изменением сигнала IL-6. Однако механизмы, ведущие к увеличению фосфорилации ПКБ, по-прежнему плохо понимаются. Здесь мы изучили выражение фосфатазы и

Совпадение в аннотации оригинала
The regulation of T cell-mediated immune responses is essential for maintaining immune homeostasis and preventing autoimmune diseases. In mu … l for effective immune regulation of T cells, and suggest its dysregulation contributes to impaired immune tolerance in MS.

Autoantibodies to Perilipin-1 Define a Subset of Acquired Generalized Lipodystrophy.

Acquired lipodystrophy is often characterized as an idiopathic subtype of lipodystrophy. Despite suspicion of an immune-mediated pathology, biomarkers such as autoantibodies are generally lacking. Here, we used an unbiased proteome-wide screening approach to identify autoantibodies to the adipocyte-specific lipid droplet protein perilipin 1 (PLIN1) in a murine model of autoimmune polyendocrine syndrome type 1 (APS1). We then tested for PLIN1 autoantibodies in human subjects with acquired lipodystrophy with two independent severe breaks in immune tolerance (including APS1) along with control su…

A replicating LCMV-based vaccine for the treatment of solid tumors.

Harnessing the immune system to eradicate tumors requires identification and targeting of tumor antigens, including tumor-specific neoantigens and tumor-associated self-antigens. Tumor-associated antigens are subject to existing immune tolerance, which must be overcome by immunotherapies. Despite many novel immunotherapies reaching clinical trials, inducing self-antigen-specific immune responses remains challenging. Here, we systematically investigate viral-vector-based cancer vaccines encoding a tumor-associated self-antigen (TRP2) for the treatment of established melanomas in preclinical mou…

CD4+CD25-FoxP3+ T cells: a distinct subset or a heterogeneous population?

In addition to generating effective immunity against infectious agents, the immune system helps to fight against different noninfectious human diseases while maintaining the balance between self and non-self discrimination. The breakdown of tolerance in autoimmune diseases or sustainable tolerance in an abnormal microenvironment such as chronic inflammation may initiate the process of malignancy. Immune system regulation is controlled by a complex, dynamic network of cells and mediators. Understanding the cellular and molecular basis of immune regulation provides better insight into the mechan

Minireview: host defence in invasive aspergillosis.

Aspergillus is a saprophytic fungus, which mainly becomes pathogenic in immunosuppressed hosts. A failure of host defences results in a diverse set of illnesses, ranging from chronic colonisation, aspergilloma, invasive disease and hypersensitivity. A key concept in immune responses to Aspergillus species is that host susceptibility determines the morphological form, antigenic structure and physical location of the fungus. Traditionally, innate immunity has been considered as a first line of defence and activates adaptive immune mechanisms by the provision of specific signals; innate and adapt

Donor-reactive T-cell stimulation history and precursor frequency: barriers to tolerance induction.

Blockade of T-cell costimulatory pathways represents a potent and specific method of preventing naïve antidonor T-cell responses after transplantation in mouse, monkey, and man. However, numerous studies have shown that the presence of donor-reactive memory T cells in the recipient poses a sometimes insurmountable barrier to long-term graft survival and tolerance induction. Here, we discuss the ways in which donor-reactive memory T cells may arise from environmental exposure to pathogens. Pathogen-specific memory T cells, by virtue of the inherent degeneracy of T-cell receptor recognition of p

Wharton's Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro.

Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantati…

Immune complications and their management in inherited and acquired bleeding disorders.

Disorders of coagulation, resulting in serious risks for bleeding, may be caused by autoantibody formation or by mutations in genes encoding … VWF]). The main strategies that have emerged to address these immune responses include (1) clinical immune tolerance induction (ITI) protocols; (2) immune suppression therapies (ISTs); and (3) the development of drugs that can improve hemostasis while bypassing the antibodies against coagulation factors altogether (some of these nonfactor therapies/NFTs are antibo …

FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development.

B cell development relies on stringent checkpoints that ensure immune competence and eliminate autoreactive clones. Transitional B cells (B220+CD93+), which emerge from the bone marrow, migrate to the spleen and differentiate into follicular (FO) or marginal zone (MZ) B cells, a process governed by B cell receptor (BCR) signaling strength, metabolic fitness, and survival cues. Here, we identify Folliculin Interacting Protein 1 (Fnip1) as a key regulator of this developmental transition. Using conditional Fnip1-deficient mice (Fnip1fl/flCD21Cre), loss of Fnip1 results in a developmental arrest

Heat shock proteins and their immunomodulatory role in inflammatory arthritis.

Autoimmune diseases, including inflammatory arthritis, are characterized by a loss of self-tolerance, leading to an excessive immune responses and subsequent ongoing inflammation. Current therapies are focused on dampening this inflammation, but a permanent state of tolerance is seldom achieved. Therefore, novel therapies that restore and maintain tolerance are needed. Tregs could be a potential target to achieve permanent immunotolerance. Activation of Tregs can be accomplished when they recognize and bind their specific antigens. HSPs are proteins present in all cells and are upregulated dur

Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells.

Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothi…

The immunologic basis for gastrointestinal food allergy.

PURPOSE OF REVIEW: Food allergies are common in children, although rare in adults. They can be life threatening via anaphylaxis, especially to peanut, and cause distress to children and parents because of the disease itself, and then through the difficulty of pursuing a strict elimination diet. In parents/carers and adults, this has significant impact on quality of life. The purpose of this review is to determine the therapeutic potential and current treatments for these conditions by understanding and manipulating the immune response. RECENT FINDINGS: The single largest change in attitude to

Insights into type 1 diabetes from the autoimmune polyendocrine syndromes.

PURPOSE OF REVIEW: Advances in human genetics and investigations in animal models of autoimmune disease have allowed insight into the basic mechanisms of immunologic tolerance. These advances allow us to understand the pathogenesis of type 1 diabetes and other autoimmune diseases as never before. Here, we discuss the tolerance mechanisms of the autoimmune polyendocrine syndromes and their relevance to type 1 diabetes. RECENT FINDINGS: Defects in central tolerance with alteration of self-antigen expression levels in the thymus are a potent cause of autoimmunity. Peripheral tolerance defects th