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Anti-TIF1γ antibody-positive dermatomyositis associated with nivolumab administration in a patient with advanced oesophageal squamous cell carcinoma: A case report and literature review.

We report a case of anti-transcriptional intermediary factor 1γ antibody-positive dermatomyositis following nivolumab treatment. The patient was successfully treated with pulse steroid therapy and high-dose intravenous immunoglobulin, followed by oral glucocorticoid treatment. Immune checkpoint inhibitors, such as nivolumab, may induce not only myositis as an immune-related adverse event but also dermatomyositides as a paraneoplastic syndrome by distracting immune tolerance. Differentiating between pathologies is warranted if patients develop myositis after immune checkpoint inhibitor administ…

Host resources and parasite traits interact to determine the optimal combination of host parasite-mitigation strategies.

Organisms have evolved diverse strategies to manage parasite infections. Broadly, hosts may avoid infection by altering behaviour, resist infection by targeting parasites or tolerate infection by repairing associated damage. The effectiveness of a strategy depends on interactions between, for example, resource availability, parasite traits (virulence, life-history) and the host itself (nutritional status, immunopathology). To understand how these factors shape host parasite-mitigation strategies, we developed a mathematical model of within-host, parasite-immune dynamics in the context of helmi

Clinical Features and T Cell Immune Characteristics of Postpartum Hepatitis Flare in Pregnant Women With HBeAg-Positive Chronic HBV Infection.

BACKGROUND: The extent of the increase in postpartum alanine transaminase (ALT) varies significantly among pregnant women in the immune tolerance stage of nucleoside analogue (NA) intervention, so this study is an attempt to analyze the clinical features of patients with and without postpartum hepatitis flare and preliminarily explore the differences in their immune functions. METHODS: Pregnant women with a gestational age of 24-28 w and in the immune tolerance stage of NA intervention for hepatitis B virus (HBV) infection were included and divided into a hepatitis group (Group 1) and a nonhe…

An Evaluation of the Impact of PD-1 Pathway Blockade on Reproductive Safety of Therapeutic PD-1 Inhibitors.

This report discusses the principles of reproductive toxicity risk assessment for biopharmaceuticals blocking the PD-1/programmed cell death ligand 1 (PD-L1) pathway, which have been developed for the treatment of patients with advanced malignancies. The PD-1/PD-L1 pathway is a T-cell co-inhibitory pathway that normally maintains immune tolerance to self. Its role in pregnancy is to maintain immune tolerance to the fetal allograft. In cancer patients, this signaling pathway is hijacked by some neoplasms to avoid immune destruction. PD-1/PD-L1-blocking agents enhance functional activity of the …

Medulloblastoma immune microenvironment resembles early brain development and reveals novel basophil- B cell- associated signatures.

BACKGROUND: Medulloblastoma (MB) is the most common malignant pediatric brain tumor; yet, the mechanisms underlying immune evasion remain po … onventional immune surveillance mechanisms. These findings suggest that MB may co-opt developmental immune tolerance programs and highlight basophil - B cell interactions as potential therapeutic targets. The developmental similarity provides new insights into MB pathogenesis and immune evasion strategies.

Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-induced Immunotolerance.

BACKGROUND & AIMS: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected wi…

Immune checkpoint molecules beyond PD-1 and CTLA-4: emerging targets in autoimmune diseases and cancer immunotherapy.

BACKGROUND: Immune checkpoint molecules are pivotal regulators of immune activation and tolerance, playing critical roles in cancer, autoimmunity, infectious diseases, and transplantation. While programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) remain the most extensively studied checkpoints, immune checkpoint receptors beyond PD-1 and CTLA-4, including LAG-3, TIM-3, TIGIT, VISTA, BTLA, CD160, and CD96 have expanded our understanding of immune regulation. These pathways not only mediate immune evasion in tumors but also contribute to impaired toler

Taurine up-regulated 1: A dual regulator in immune cell-mediated pathogenesis of human diseases.

Taurine up-regulated 1 (TUG1) is a long non-coding RNA (lncRNA) that plays a significant role in the pathogenesis of both cancer and non-can … y of specific transcription factors. It fosters tumor development by promoting the establishment of immune tolerance within the tumor microenvironment. This immune tolerance is associated with TUG1's regulation of immune checkpoint molecules, which enhances the infiltration of pro-tumor immune cells (e.g., regulatory T cells, M2 macrophages, neutrophils, and dendr …

Immune cells in the female reproductive tract.

The female reproductive tract has two main functions: protection against microbial challenge and maintenance of pregnancy to term. The upper reproductive tract comprises the fallopian tubes and the uterus, including the endocervix, and the lower tract consists of the ectocervix and the vagina. Immune cells residing in the reproductive tract play contradictory roles: they maintain immunity against vaginal pathogens in the lower tract and establish immune tolerance for sperm and an embryo/fetus in the upper tract. The immune system is significantly influenced by sex steroid hormones, although le…

Immunology of neonatal gene transfer.

Gene therapy could result in the permanent correction or amelioration of the clinical manifestations of many genetic diseases. However, immune responses to the therapeutic protein pose a significant hurdle for successful gene therapy. Problematic immune responses can include the development of a cytotoxic T lymphocyte (CTL) response that results in the destruction of genetically-modified cells and/or the formation of antibodies directed against the therapeutic protein. One approach to avoid an immune response is to perform gene therapy in newborns, which takes advantage of the fact that the im

Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance.

Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine

Symposium review: Immunological detection of the bovine conceptus during early pregnancy.

Infertility and subfertility reduce the economic viability of dairy production. Inflammation reduces conception rates in dairy cattle, but surprisingly little information exists about the populations and the functions of immune cells at the conceptus-maternal interface during the periattachment period in dairy cattle. Early pregnancy is accompanied by immune stimulation at insemination and conceptus secretion of IFN-τ, pregnancy-associated glycoproteins, prostaglandins, and other molecules whose effects on immune function during early pregnancy have not been determined. Our working hypothesis

Survival strategies of Borrelia burgdorferi, the etiologic agent of Lyme disease.

To fight, flee or hide are the imperatives of long-term survival by an infectious microbe. Active immune suppression, induction of immune tolerance, phase and antigenic variation, intracellular seclusion, and incursion into immune privileged sites are examples of survival strategies of persistent pathogens. Here we critically review the supporting evidence for possible stratagems utilized by Borrelia burgdorferi, the spirochete that causes Lyme disease, to persist in the mammalian host.

Pregnancy-associated thyroid disorders: the role of genetic, epigenetic, and oxidative stress factors.

Thyroid inflammation during pregnancy, particularly Hashimoto's thyroiditis (HT) and postpartum thyroiditis (PPT), has a strong genetic and epigenetic basis. Susceptibility to these conditions is associated with specific HLA haplotypes (HLA-DR3, DR4, DR5) and immune-regulatory genes, including CTLA-4, PTPN22, FOXP3, as well as thyroid-specific genes such as TSHR, TG, and TPO. CTLA-4 polymorphism (CT60) is linked to increased thyroid autoantibody production, while PTPN22 R620W variant disrupts immune tolerance, exacerbating autoreactive lymphocyte activation.Epigenetic modifications play a cruc…

PI3K at the crossroads: choosing B-cell activation or tolerance.

Phosphoinositide 3-kinase (PI3K) mediates signaling downstream of many receptors expressed by B cells. Studies in both mice and humans have shown that PI3K plays a critical role in B-cell development, activation, and tolerance. Indeed the key role of PI3K in regulating activation versus tolerance is demonstrated by patients with genetic variants that cause increased PI3K signaling, which results in an immune dysregulatory disorder characterized by a range of manifestations including lymphoproliferation and autoantibody production. Interestingly, PI3K signaling also plays an essential role in m

Аутоиммунное заболевание: генетическая восприимчивость, экологические факторы и регулирование иммунной дисдукции. Где мы можем развивать терапию?

Аутоиммунные заболевания представляют собой разнообразную группу хронических расстройств, характеризующихся неадекватной иммунной реакцией на самоантигены, приводящей к стойкому воспалению и разрушению тканей. Эти условия, затрагивающие примерно 7-10% населения мира, включают как системные, так и специфические для органов организмы, такие, как системная волчанка (SLE), ревматоидный артрит (RA), диабет типа 1 (T1D) и множественный склероз (MS). Несмотря на их клиническую неоднородность, аутоиммунные заболевания имеют общую этиологическую структуру, которая включает конвергенцию генетической пре

Совпадение в аннотации оригинала
Autoimmune diseases are a diverse group of chronic disorders characterized by inappropriate immune responses against self-antigens, resultin … s) conjugated to IL-2 or anti-CD25 antibodies. This approach selectively restores Treg function and immune tolerance without inducing systemic immunosuppression. By focusing on immune restoration rather than suppression, This therapy could provide an off the shelf therapy for many different autoimmune diseases.

The preclinical data and immunologic rationale for hematopoietic stem cell transplantation in autoimmunity.

The development of autoimmune diseases (ADs) is thought to be caused by a dysfunction of the intrinsic ability of our immune system for "self-nonself" discrimination. Following the breakdown of "self-tolerance," an orchestrated immune cascade develops, involving B- and T-lymphocytes and autoantibodies that target self-antigens. An imbalance of the regulatory immune network and a suitable genetic background, along with external (infectious and environmental) triggers, are all important contributors to the outbreak of clinical autoimmunity. Immunotherapies for ADs can be classified into treatmen

Mathematical modeling of N-803 treatment in SIV-infected non-human primates.

Immunomodulatory drugs could contribute to a functional cure for Human Immunodeficiency Virus (HIV). Interleukin-15 (IL-15) promotes expansion and activation of CD8+ T cell and natural killer (NK) cell populations. In one study, an IL-15 superagonist, N-803, suppressed Simian Immunodeficiency Virus (SIV) in non-human primates (NHPs) who had received prior SIV vaccination. However, viral suppression attenuated with continued N-803 treatment, partially returning after long treatment interruption. While there is evidence of concurrent drug tolerance, immune regulation, and viral escape, the relat

Short-chain fatty acids regulate T cell heterogeneity to alleviate recurrent spontaneous abortion.

BACKGROUND AND PURPOSE: The aetiology of recurrent spontaneous abortion (RSA) is multifactorial, with immune factors playing a critical role. Gut microbiota and its metabolites have been found to participate in host immune regulation. This study explores the role of gut microbiota-derived short-chain fatty acids (SCFAs) in immune tolerance in RSA. EXPERIMENTAL APPROACH: Single-cell sequencing was used to analyse the cell profile of RSA patients. 16S rDNA sequencing was used to analyse the gut microbiota structure. Faecal microbiota transplantation (FMT) was used to explore the role of the gut…

Targeting FOXP3 and Regulatory T Cells in Systemic Lupus Erythematosus: Emerging Therapeutic Strategies and Clinical Prospects.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-system involvement, and its pathogenesis is complex, involving abnormalities of multiple immune cells and molecules. In recent years, the role of the transcription factor Forkhead Box P3 (FOXP3) in SLE has attracted much attention. FOXP3, a crucial indicator of regulatory T cells (Tregs), is essential for maintaining immune tolerance and suppressing excessive immune responses. This review systematically elucidates the multi-tiered regulatory networks that control FOXP3 expression at the transcriptional, epigenetic, a…