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Maternal and Fetal HLA Heterozygosity in Preeclampsia: Insights From a Large Multi-Ancestry Pregnancy Cohort.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity, with immune dysregulation at the maternal-fetal interface central to its pathogenesis. The highly polymorphic HLA region mediates maternal immune tolerance of the semi-allogeneic fetus, yet the contribution of HLA diversity to PE risk remains poorly defined. Whether the HLA heterozygote advantage observed in other immune disorders is relevant to PE has not been systematically evaluated. Using data from the multi-ancestry TOPMed Boston-Colombia Collaborative for Adverse Pregnancy Outcomes (n = 12,790; 4770 PE, 8020 control…

Prognostic impact of CT-defined sarcopenia and prognostic nutritional index in immune checkpoint inhibitor-treated head and neck squamous cell carcinoma: A systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) have become a standard treatment for recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), yet survival outcomes remain highly heterogeneous, and reliable host-related prognostic biomarkers are lacking in the immunotherapy era. Growing evidence suggests that nutritional status and body composition may influence immune competence, treatment tolerance, and survival, although data specific to ICI-treated HNSCC are fragmented. We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines to evaluate the progn

A single-cell transcriptomic atlas of the pigtail macaque placenta in late gestation.

BACKGROUND: The placenta is a complex organ with multiple immune and non-immune cell types that promote fetal tolerance and facilitate the transfer of nutrients and oxygen. The nonhuman primate (NHP) is a key experimental model for studying human pregnancy complications, in part due to similarities in placental structure, which makes it essential to understand how single-cell populations compare across the human and NHP maternal-fetal interface. We constructed a single-cell RNA-Seq (scRNA-Seq) atlas of the placenta from the pigtail macaque (Macaca nemestrina) in the third trimester, comprising

Peripheral immune network-directed dissection of lymph node regions (iLND): Novel surgical approach for the regional assessment and therapy of vulvar carcinoma.

BACKGROUND: Approximately 30% of vulvar cancer patients present with node-positive disease and poor prognosis under current standards. Sentinel lymph node biopsy carries a false-negative rate exceeding 2%, often with fatal consequences, and recurrence-free survival after surgery and adjuvant radiotherapy remains below 40%. The concept of ontogenetic cancer fields links regional metastasis to pathological peripheral immune tolerance and forms the basis for immune network-directed lymph node dissection (iLND), a novel, purely surgical approach to regional disease control. METHODS: In the prospe…

Neuropilins in Multiple Sclerosis: Dual Roles of NRP-1 in Neuroinflammation and Neuroprotection.

Neuropilins (NRPs), particularly NRP-1, are multifunctional co-receptors involved in neuroinflammatory and neuroprotective processes. Altered NRP expression has been observed in multiple sclerosis (MS) lesions and peripheral circulation, suggesting early involvement in disease progression. This review addresses the dual role of NRPs in MS and experimental autoimmune encephalomyelitis (EAE), emphasizing expression patterns, signaling pathways, and therapeutic interventions. NRP-1 is expressed by endothelial cells, microglia, and macrophages, while Sema3A, a key ligand, is produced by reactive a

Gut Microbiota and Inflammatory Diseases: Emerging Insights and Therapeutic Perspectives. A Report From the Spanish Inflammatory Diseases Network.

The gut microbiota constitutes a highly complex ecosystem that plays a pivotal role in maintaining human health and modulating the immune re … as short-chain fatty acids (SCFAs) and secondary bile acids in sustaining epithelial integrity and immune tolerance. Altered microbiota profiles are associated with increased intestinal permeability, systemic inflammation, and autoimmune conditions including multiple sclerosis, rheumatoid arthritis, and inflammatory eye disease. Early-life establishment of microb …

Genetic and Molecular Determinants of Cancer Therapy-Related Cardiovascular Toxicity.

Cancer therapy-related cardiovascular toxicity (CTR-CVT) is an umbrella term for myocardial, vascular, electrical, and inflammatory complica … bition by endothelial dysfunction and hypertension; immune checkpoint inhibitor toxicity by loss of immune tolerance; and radiotherapy injury by endothelial and microvascular damage with progressive fibrosis. Mitochondrial dysfunction, oxidative stress, inflammation, calcium dysregulation, apoptosis, and ferroptosis frequently act as downstream or amplifying pathw …

TRANQUIL уменьшает аутоиммунную демииляцию и подавляет нейроинфламматический сигнал в экспериментальном аутоиммунном энцефаломиелите.

Нейроинфламмация, движущаяся автоматически реактивными клетками Т и активированными глиальными популяциями, лежит в основе патогенеза множественного склероза (MS), однако нынешняя иммунодуляторная терапия редко восстанавливает долгосрочную иммунную терпимость и часто вызывает широкое иммуноусилительное воздействие. Ранее мы сконструировали слабый штамм брюселлы ΔvjbR, выражающий tnaA, позволяющий создать производство триптофана метаболита индола, модулятора активации антигенной клетки (APC) и дифференциации Т-клеток. Здесь мы проверили, улучшит ли этот штамм (TRANQUIL - Technology for Reprogra

Совпадение в аннотации оригинала
Neuroinflammation driven by autoreactive T cells and activated glial populations underlies the pathogenesis of multiple sclerosis (MS), yet current immunomodulatory therapies rarely restore durable immune tolerance and often cause broad immunosuppression. We previously engineered an attenuated Brucella melitensis ΔvjbR strain expressing tnaA, enabling consti…

Amniotic fluid glycoproteins as potential ligands for macrophage galactose-type C-type lectin and their possible implications for immunoregulation during pregnancy.

Immunity during pregnancy must be precisely balanced, because the mother's body needs to effectively fight pathogens while maintaining tolerance of the semi-allogeneic fetus. Factors that participate in achieving the proper immune balance during pregnancy include glycoproteins that expose sugar residues recognized by specific lectin receptors. Several types of lectins and their ligands have been detected at the maternal-fetal interface, and changes in their expression levels have been correlated with pregnancy complications. Although the presence of potential sugar ligands for human macrophage

Immune Checkpoint Dysregulation in Autoimmune Disorders: A Narrative Review of Therapeutic Implications.

Immune checkpoints act like dimmer switches that keep immune responses in balance. In autoimmune disease, problems usually fall into four overlapping types: weak inhibitory signals, too much co-stimulation, metabolic or epigenetic rewiring of checkpoint pathways, and a mismatch between tissue and blood findings. This narrative review focused on human and translational studies from PubMed/Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (Embase), Web of Science, and Scopus (to 2025), prioritizing tissue-based data, trials of checkpoint agonists or co-s

Immunosenescence in Kidney Transplant Recipients.

The term immunosenescence refers to the collective effects of aging on the immune system, which involves both the innate and the adaptive immunity and plays a dominant role in patients' morbidity and mortality. Senescent T lymphocytes are in a state of replicative arrest and have several unique features: they typically lack costimulatory molecules, they express shortened telomeres, and they have the capacity to produce large amounts of proinflammatory cytokines. The B-lymphocyte compartment and the cells of the innate immune system also demonstrate important changes due to aging. The immunosen

PEDF-Expressing mesenchymal stem cells restore ovarian function via Tim-3-Mediated immune modulation in primary ovarian failure.

BACKGROUND: Primary ovarian failure (POF), characterized by premature ovarian dysfunction, remains a therapeutic challenge due to limited in … that PEDF-engineered BMSCs rejuvenate ovarian function by dual mechanisms: enhancing Treg-mediated immune tolerance via the Tim-3/Gal-9 axis and promoting follicular survival. These findings position BMSCs-PEDF as a transformative, mechanism-driven therapy for POF, with broad implications for autoimmune-related infertility.

Трег-приемлемость к кладрипину привела к разрушению коррелирует с терапией у пациентов с множественным склерозом.

ИСТОРИЯ ВОПРОСА И ЦЕЛИ: Иммунная реконструктивная терапия при множественном склерозе (МС) основана на избирательном сокращении лимфоцитов, за которым следуют перенаселение и сохранение иммунной терпимости. Среди этих методов кладрипин — аденозиновый аналог, который мешает разделению клеток и истощает несколько подтипов лимфоцитов. Регулирующие Т клетки (Tregs), физиологически предназначенные для иммунного подавления, не функционируют в контексте MS. В этом исследовании мы изучили влияние кладрибина на динамику Трега и фенотипа.МЕТОДЫ: В vivo на периферийной крови пациентов с склерозом (n = 11)

Совпадение в аннотации оригинала
BACKGROUND AND OBJECTIVES: Immune reconstitution therapies for multiple sclerosis (MS) are based on selective lymphocyte reduction, followed by repopulation and rescue of immune tolerance. Among these therapies, cladribine is an adenosine analog that interferes with cell division and depletes several lymphocyte subtypes. Regulatory T cells (Tregs), physiolog…

Unlocking the secrets of Hofbauer cells in placental (patho-) physiology: Isolation and quality assessment in human term placenta.

INTRODUCTION: Hofbauer cells (HBCs) are macrophages of fetal origin that reside in the villous tissue. They are the only immune cells within healthy villi. While HBCs perform innate immune functions such as phagocytosis and antigen presentation, they are increasingly recognized for their diverse roles in placental physiology e.g. vascular functionality, tissue homeostasis, tolerance. Consequently, HBCs are of utmost interest in a variety of non-physiological placental conditions. ISOLATION: Villous tissue is collected freshly after delivery and finely minced. The resulting tissue is digested

Fetal ezrin expression affects macrophages and regulatory T cells in mouse placental decidua.

Ezrin is a cross-linker protein between membrane proteins and cytosolic actin, abundantly expressed in the placenta among the ERM protein family. Ezrin gene knockout mice exhibit fetal growth restriction after gestational day (GD) 15.5. This study aimed to clarify the effect of ezrin on immune cells that influence fetal growth and immune tolerance. Ezrin heterozygous knockout (Ez+/-) mice were interbred, and the gene expressions and immune cell distributions in the placentas of wild-type (Ez+/+) and ezrin knockout (Ez-/-) fetuses were analyzed. IL-6 expression in the placenta of Ez-/- fetuses …

Exosomes in infectious diseases: insights into leishmaniasis pathogenesis, immune modulation, and therapeutic potential.

Leishmaniasis continues to be a critical international health issue due to the scarcity of efficient treatment and the development of drug tolerance. New developments in the research of extracellular vesicles (EVs), especially exosomes, have revealed novel disease management approaches. Exosomes are small vesicles that transport lipids, nucleic acids, and proteins in cell signalling. Its biogenesis depends on several cellular processes, and their functions in immune response, encompassing innate and adaptive immunity, underline their function in the pathogen-host interface. Exosomes play a sig

Regulatory B Cells-Immunopathological and Prognostic Potential in Humans.

The aim of the following review is to shed light on the putative role of regulatory B cells (Bregs) in various human diseases and highlight their potential prognostic and therapeutic relevance in humans. Regulatory B cells are a heterogeneous group of B lymphocytes capable of suppressing inflammatory immune reactions. In this way, Bregs contribute to the maintenance of tolerance and immune homeostasis by limiting ongoing immune reactions temporally and spatially. Bregs play an important role in attenuating pathological inflammatory reactions that can be associated with transplant rejection, gr

Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.

As part of our work to develop small-molecule inhibitors (SMIs) of the CD40-CD40L(CD154) costimulatory protein-protein interaction, here, we … and functional long after terminating treatment, suggesting the possibility of inducing operational immune tolerance via inhibition of the CD40-CD40L axis. SMI-treated mice maintained the structural integrity and function of their islet allografts with concomitant reduction in immune cell infiltration as evidenced by direct longitudinal imaging in situ. Furthermor …

Vascular disease persistence in giant cell arteritis: are stromal cells neglected?

Giant cell arteritis (GCA), the most common systemic vasculitis, is characterised by aberrant interactions between infiltrating and resident cells of the vessel wall. Ageing and breach of tolerance are prerequisites for GCA development, resulting in dendritic and T-cell dysfunction. Inflammatory cytokines polarise T-cells, activate resident macrophages and synergistically enhance vascular inflammation, providing a loop of autoreactivity. These events originate in the adventitia, commonly regarded as the biological epicentre of the vessel wall, with additional recruitment of cells that infiltra

The intestinal microenvironment shapes macrophage and dendritic cell identity and function.

The gut comprises the largest body interface with the environment and is continuously exposed to nutrients, food antigens, and commensal microbes, as well as to harmful pathogens. Subsets of both macrophages and dendritic cells (DCs) are present throughout the intestinal tract, where they primarily inhabit the gut-associate lymphoid tissue (GALT), such as Peyer's patches and isolated lymphoid follicles. In addition to their role in taking up and presenting antigens, macrophages and DCs possess extensive functional plasticity and these cells play complementary roles in maintaining immune homeos