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Immunodeficiencies and CFTR dysfunction: results from a systematic screening in a cohort of adults with cystic fibrosis and CFTR-related disorders.

BackgroundImmunodeficiencies (IDs) are conditions caused by immune system dysfunctions which predispose to chronic infections. Cystic fibrosis (CF) patients are characterized by the presence of bronchiectasis filled with hyper-viscous secretions that constitute the ideal environment for infections. Although CF and IDs might share similarities in the pathophysiological mechanism of bronchiectasis development, they each offer different treatment options. We hypothesize that the introduction of a bundle of tests would increase the number of ID diagnoses among adults with Cystic Fibrosis Transmemb

The role of autophagy in cancer: from molecular mechanism to therapeutic window.

Autophagy is a cellular degradation process that plays a crucial role in maintaining metabolic homeostasis under conditions of stress or nutrient deprivation. This process involves sequestering, breaking down, and recycling intracellular components such as proteins, organelles, and cytoplasmic materials. Autophagy also serves as a mechanism for eliminating pathogens and engulfing apoptotic cells. In the absence of stress, baseline autophagy activity is essential for degrading damaged cellular components and recycling nutrients to maintain cellular vitality. The relationship between autophagy a

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… Major histocompatibility complex (MHC) class II molecules present antigenic, foreign proteins on antigen-presenting cells, activating CD4+ T-cells and CD8+ T cells, and natural killer (NK) cells create cytolytic granules, which autophagy encourages destruction ( 29 ). … Notably, despite the distinct mechanisms of action, both class I and II major histocompatibility complex (MHC) processing require activation of autophagy, even though a combination of starvation and rapamycin therapy induces autophagy, which reduces class II protein presentation ( 153 , 228 ). …

Decoding Cancer Risk: Understanding Gene-Environment Interactions in Cancer Development.

While lifestyle choices or behavioral patterns remain the most significant factors influencing cancer risk, environmental exposure to certain chemicals, both manufactured and natural, may also contribute to an individual's likelihood of developing cancer. This interplay of factors, coupled with an aging demographic and shifting lifestyle patterns, has led to an increasing prevalence of cancer in recent years. This study examines the environmental and behavioral factors that contribute to anomalies in the immune system and increase the risk of developing cancer. Significant environmental and oc

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… EBV: Epstein-Barr virus; CXCL-11: C-X-C motif chemokine ligand 11; ER: endoplasmic reticulum; TCR: T-cell receptor; MHC: major histocompatibility complex; NKG2D: natural killer group 2D; MICB: MHC class I chain-related molecule B; IL-6R: interleukin-6 receptor; NK cell: natural killer cell; PD-L1: programmed …

Ирисин сдерживает нейроинфламму в мышечном экспериментальном аутоиммунном энцефаломиэлите, регулируя микроглию активации.

ВСТУПЛЕНИЕ: Множественный склероз представляет собой хроническое аутоиммунное демиелионирующее расстройство, в основном затрагивающее белую материю центральной нервной системы, с экспериментальным аутоиммунным энцефаломиелитом (EAE), который служит классической моделью животных. Irisin — гликозилированный белок, полученный из протеолитического декольте фибронектина типа III, содержащего домен 5, играет важную роль в регулировании метаболизма и воспалительной модуляции в организме.МЕТОДЫ: В рамках этого исследования мы систематически изучали терапевтические последствия и основополагающий механи

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… These activated microglia upregulate the express of proinflammatory markers, including TMEM119, iNOS, major histocompatibility complex II (MHC II), CD40, CD45, CD68 and CD86 ( Zrzavy et al., 2017 ). …

Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research.

T lymphocytes (T cells) are essential components of the adaptive immune system that play a vital role in identifying and eliminating infected and tumor cells. In tumor immunotherapy, T cells have emerged as a promising therapeutic strategy due to their high specificity, potent cytotoxic capability, long-lasting immune memory, and adaptability within immunotherapeutic approaches. However, tumors can evade the immune system by depleting T cells through various mechanisms, such as inhibitory receptor signaling, metabolic exhaustion, and physical barriers within the tumor microenvironment. This re

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… Based on existing research, Liang et al. concluded that TCRs specifically recognize antigen peptides presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells and convert extracellular recognition signals into intracellular signals. …

Hemostasis at the edge between physiology and cancer.

Hemostasis lies at the edge between physiology and cancer, where the coagulation cascade-initiated by tissue factor, thrombin generation, and fibrin deposition-shifts from vascular repair to tumor promotion. The interplay between coagulation and cancer is now recognized as a two-way street, with tumor cells activating the clotting system and coagulation components feeding back to promote malignancy. Tumor cells not only foster proliferation and invasion by overexpressing tissue factor and activating Protease-Activated Receptors (PAR1/PAR2) signalling, but they also induce endothelial cells and

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… Platelet-derived transforming TGF-β suppresses NK cell cytotoxicity and downregulates activation receptors, while platelet transfer of major histocompatibility complex class I (MHC-I) molecules to tumor cells can cause a “pseudo-self” phenotype that further compromises immune clearance [ 64 ]; - Platelet … Histocompatibility Complex Class I Macrophages 2 Neutrophil Extracellular Traps Natural Killer Overall survivals Plasminogen Activator Inhibitor–1 Protease-Activated Receptors Platelet-Derived Growth Factor P-glycoprotein Prothrombin Time Thrombin-Antithrombin Complexes Tumor Cell-Induced …

Abscopal Effect in Radiation Therapy: The Immune Mechanisms and Clinical Advances.

The abscopal effect is a systemic antitumor response to localized radiotherapy (RT) that has emerged as a central focus in the era of immunotherapy. Clinical evidence demonstrates that local RT can induce regression of distant, nonirradiated metastases, including cases of complete remission. However, the effect remains unpredictable, with marked variation in clinical outcomes ranging from complete regression to paradoxical progression. The mechanistic basis for this heterogeneity and optimal strategies to enhance abscopal effects remain incompletely understood. This review synthesizes current

The Interplay between Immune System and Microbiota in Osteoporosis.

Osteoporosis is a disease characterized by low bone mass and alterations of bone microarchitecture, with an increased risk of fractures. It is a multifactorial disorder that is more frequent in postmenopausal women but can be associated to other diseases (inflammatory and metabolic diseases). At present, several options are available to treat osteoporosis trying to block bone reabsorption and reduce the risk of fracture. Anyway, these drugs have safety and tolerance problems in long-term treatment. Recently, gut microbiota has been highlighted to have strong influence on bone metabolism, becom

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… Furthermore, the lack of estrogens increases the expression of Class II TransActivator (CIITA), a transcriptional factor involved in the upregulation of major histocompatibility complex class II on macrophages, improving the antigen presentation [ 45 ]. …

Interventional Cardio-Oncology: Adding a New Dimension to the Cardio-Oncology Field.

The management of cardiovascular disease in patients with active cancer presents a unique challenge in interventional cardiology. Cancer patients often suffer from significant comorbidities such as thrombocytopenia and coagulopathic and/or hypercoagulable states, which complicates invasive evaluation and can specifically be associated with an increased risk for vascular access complications. Furthermore, anticancer therapies cause injury to the vascular endothelium as well as the myocardium. Meanwhile, improvements in diagnosis and treatment of various cancers have contributed to an increase i

The investigation of oncolytic viruses in the field of cancer therapy.

Oncolytic viruses (OVs) have emerged as a potential strategy for tumor treatment due to their ability to selectively replicate in tumor cells, induce apoptosis, and stimulate immune responses. However, the therapeutic efficacy of single OVs is limited by the complexity and immunosuppressive nature of the tumor microenvironment (TME). To overcome these challenges, engineering OVs has become an important research direction. This review focuses on engineering methods and multi-modal combination therapies for OVs aimed at addressing delivery barriers, viral phagocytosis, and antiviral immunity in

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… This modification also leads to an increase in the expression of major histocompatibility complex II (MHC II) in antigen-presenting cells, thereby altering the immune status and systemic immune response within the TME. …

Hematopoietic stem cell expansion and generation: the ways to make a breakthrough.

Hematopoietic stem cell transplantation (HSCT) is the first field where human stem cell therapy was successful. Flooding interest on human stem cell therapy to cure previously incurable diseases is largely indebted to HSCT success. Allogeneic HSCT has been an important modality to cure various diseases including hematologic malignancies, various non-malignant hematologic diseases, primary immunodeficiency diseases, and inborn errors of metabolism, while autologous HSCT is generally performed to rescue bone marrow aplasia following high-dose chemotherapy for solid tumors or multiple myeloma. Re

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… Earlier failure of human HSCT in 1950s was due to a lack of understanding about major histocompatibility complex (MHC) molecules. After considerable trials and failures in dogs, researchers developed molecular techniques to type human MHC (HLA) in order to find matched human donors. …

Связь между окисляющим стрессом, митохондриальной дисфункцией, железным метаболизмом и микроглией в множестве склерозов: обзор нарации.

В последние годы в патогенезе множественного склероза особое внимание уделяется митохондриальным процессам, влияющим на начало заболевания. Окисляющий стресс будет одним из последствий митохондриальной дисфункции, и его воздействие на ткани мозга хорошо описано. Микроглия, как макрофаж мозга, имеет важную функцию в удалении нежелательных метаболитов, а также железа, который является усилителем окислительного стресса. Существуют новшества с точки зрения связи между этими процессами, которые в большей степени перенаправляют исследования на сам процесс нейродегенерации, с тем чтобы больше не дела

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… Interferon beta reduces Major histocompatibility complex (MHC) class II expression on microglia but increases proinflammatory mediators. Glatiramer acetate, dimethyl fumarate, and teriflunomide (indirect effect) also had an inhibitory effect on microglia. …

The race is on: bispecifics vs CAR T cells in B-cell lymphoma.

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… Both of these therapies result in target cell lysis independent of T-cell receptor specificity and major histocompatibility complex presentation of a tumor antigen. 1 BiAbs combine the antigen binding regions from 2 different single chain antigen binding domains to form an antibody construct binding, …

T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occ

Роль Ocrelizumab в модуляции гена и микроRNA-выражения в множестве склероза.

Множественный склероз — это аутоиммунное нейродегенеративное заболевание и одна из наиболее серьезных проблем в современной неврологии, которая затрагивает приблизительно 2,8 миллиона человек во всем мире. В качестве многофакторного состояния подверженность НР может быть вызвана сочетанием генетических и экологических факторов. Нынешние стратегии лечения направлены на предотвращение острых приступов, медленного развития заболеваний и смягчение симптомов. Окрелизумаб, моноклонный антител, направленный на CD20, продемонстрировал свою эффективность в клинических испытаниях, уменьшив как активност

Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.

In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor w

Conjunctival HLA-DR and CD8 expression detected by impression cytology in ocular graft versus host disease.

PurposeTo assess the expression of human leucocyte antigen (HLA)-DR in epithelial cells and cluster of differentiation (CD8)-positive lymphocytes as possible markers of chronic ocular graft versus host disease (cGvHD) after hematological stem cell transplantation (HSCT).MethodsTwenty-seven consecutive patients with dry-eye symptoms following HSCT (24 [89%] with peripheral blood stem cell transplantation and 3 [11%] with bone marrow transplants; 17 [63%] familiar allogenic grafts) and 19 age-matched controls were included. Conjunctival impression cytology specimens were stained for HLA-DR, cyto

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… Recently, Rojas et al. examined human leucocyte antigen (HLA)-DR, which is part of the major histocompatibility complex II and is involved in antigen presentation to immune cells, in conjunctival biopsies and found increased expression after HSCT [ 5 ]. …

The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?

Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptiv

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… These works demonstrated that murine lymphoma cells with low or absent expression of genes encoded by the major histocompatibility complex (MHC) class I were lysed very efficiently by NK cells, while cells expressing such molecules were resistant to lysis [ 13 , 14 ]. … KIRs generally recognize class I major histocompatibility complex molecules—mainly HLA-A, B, and C classical MHC molecules—and can be activating or inhibitory [ 49 ]. …

Integrative Multi-Omics Analysis of Multiple Sclerosis Reveals Cell-Type-Specific Regulatory Landscapes and Discordant Methylation-Expression Coupling.

Multiple sclerosis (MS) is an immune-mediated central nervous system disease with mapped genetic risk loci but unresolved cross-layer regulatory mechanisms. We harmonised 30 primary public MS datasets spanning bulk transcriptomics (552 samples, 367 MS/185 healthy control [HC]), DNA methylation arrays (475 samples, 244 MS/231 HC) with sorted-cell whole-genome bisulfite sequencing (WGBS) assessment, single-cell RNA sequencing (RNA-seq; 517,533 cells from 81 donors), and cerebrospinal fluid (CSF) and brain white-matter proteomes, and UK Biobank Pharma Proteomics Project (UK Biobank-PPP) plasma pr

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… That reference map resolved 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC) and 32 independent variants within the MHC and prioritised more than 500 candidate susceptibility genes, with statistical enrichment pointing predominantly to peripheral lymphocytes, monocytes … Histocompatibility Complex MS Multiple Sclerosis; in DIA-MS, Mass Spectrometry NAWM Normal-Appearing White Matter NES Normalised Enrichment Score NK Natural Killer (cell) NKG2A Natural Killer Group 2 member A OND Other Neurological Diseases OPC Oligodendrocyte Progenitor Cell PBMC Peripheral-Blood Mononuclear …

IgA Nephropathy: Current Treatment and New Insights.

IgA Nephropathy (IgAN) is the most common cause of primary glomerulonephritis worldwide. Despite the histopathologic hallmark of mesangial IgA deposition, IgAN is a heterogenous autoimmune disease not only in terms of clinical presentation but also in long-term disease progression. The pathogenesis of the disease is complex and includes the generation of circulating IgA immune complexes with chemical and biological characteristics that favor mesangial deposition and reaction to mesangial under-glycosylated IgA1 accumulation, which leads to tissue injury with glomerulosclerosis and interstitial

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… With technological advances in genotyping, genetic studies, in particular hypothesis-free genome-wide association studies (GWASs), have documented significant associations of IgAN with several single-nucleotide polymorphisms within or near immune-related genes such as major histocompatibility complex …