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Interplay between genetic and environmental risk factors in multiple sclerosis: what have we learned?

Genome-wide association studies have identified >230 genetic variants associated with susceptibility to multiple sclerosis and one genome-wi … d statistically significant interactions between host genetics and environmental factors beyond the major histocompatibility complex. Epigenetics (the study of non-nucleotide alterations to DNA, such as DNA methylation or histone acetylation) might provide a mechanistic framework for understanding how environmental and genetic factors interact in multiple sclerosis. Environmental …

Discovery of conserved peptide-MHC epitopes for directly alloreactive CD8+ T cells.

Mass Spectrometry allied with in-vivo generation of activated alloreactive T cell populations and tetramer screening facilitates the identification of endogenous peptides that are directly recognised in complex with allogeneic Major Histocompatibility class I (MHC I) molecules by alloreactive CD8+ T cells. We had previously used this approach for the discovery of immunogenic self-peptides presented by the allomorph H-2Kb (Kb). In this study, we identified 22 highly immunogenic self-peptides presented by H-2Kd (Kd). Peptide abundance across skin, spleen and liver samples (estimated as the produ

Isolation and characterization of mesenchymal stromal cells derived from equine ovarian follicular aspirates.

The use of mesenchymal stromal cells (MSCs) in equine reproduction is increasing its interest in the treatment of specific pathologies. MSCs … cteristic MSCs surface markers), and negative for CD45 and CD19 (hematopoietic markers), as well as major histocompatibility complex class II (MHC-II) as asessed by flow cytometry. Gene expression analysis by RT-qPCR revealed significant upregulation of the MSC-related genes THY1 and FGF2 in cultured cells compared to the native follicular aspirates, indicating the enrichment of …

BIRC2 blockade facilitates immunotherapy of hepatocellular carcinoma.

BACKGROUND: The effectiveness of immunotherapy in hepatocellular carcinoma (HCC) is limited, however, the molecular mechanism remains unclea … g to the inactivation of the non-canonical NFκB signaling pathway. This resulted in the decrease of major histocompatibility complex class I (MHC-I) expression, thereby protecting HCC cells from T cell-mediated cytotoxicity. Silencing BIRC2 using shRNA or inhibiting it with small molecules increased the sensitivity of HCC cells to immune killing. Meanwhile, BIRC2 blockade improve …

Cellular communication networks in fibrosis: Insights from the MASLD pig model.

BACKGROUND: This research aims to reveal the cellular cross talk in fibrosis liver using transgenic pigs (TG) expressing humanized risk gene … hat over 90% of macrophages in TG liver differentiated to Fate 1 (CD68hi) with higher expression of major histocompatibility complex-II molecules, proinflammatory cytokines, phagosomes, and lysosomal-related genes. Active cell interactions were found between HSCs, endothelial cells, and Fate1 macrophages. Ligand and receptor interactions, including FGF23-FGFR, PDGFs-PDGFRs, EFNA1 …

Inhibitory Effect of Propofol on Type II Inflammation in Mice with Allergic Rhinitis.

Propofol, a quick‑acting systemic anesthetic agent widely used in general anesthesia, can alleviate airway T-helper 2 (TH2) inflammation. Gr … as added, the percentage of TH2 cells significantly decreased. This effect was alleviated when anti-major histocompatibility complex class II (anti-MHC II) protein was added.  Our study provides preliminary evidence that propofol can play an inhibitive role in AR by regulating innate and adaptive immunity.

The CD38+HLA-DR+ T cells with activation and exhaustion characteristics as predictors of severity and mortality in COVID-19 patients.

BACKGROUND: The COVID-19 pandemic remains a global health challenge. Severe cases often respond poorly to standard treatments, highlighting … d IL-10 mRNA levels among all T-cell subsets. Further functional analysis demonstrated its enhanced major histocompatibility complex class II (MHC-II) cross-signaling and correspondingly enriched cytoskeletal rearrangement processes. In addition, there was dysregulated NAD+ metabolism in CD38+HLA-DR+ T cells via scRNA-seq, accompanied by elevated adenosine and decreased NAD+ leve …

Longitudinal single-cell analysis of glucagon-like peptide-2 treatment in patients with short bowel syndrome.

BACKGROUNDGlucagon-like peptide-2 (GLP-2) analogs are used clinically to enhance nutrient absorption in patients with short bowel syndrome ( … -absorbing enterocyte-Top2 and middle clusters expanded, enhancing the absorption capacity, whereas major histocompatibility complex class I/II-expressing enterocyte-Top1 cells declined, potentially modulating immune responses.CONCLUSIONThe study findings indicate that GLP-2 analogs reshape intestinal immunity and microbiota, fostering a less inflammatory environment while promot …

Prognostic impact of biomarkers in PMBCL: rationale for early integration of immune checkpoint inhibitors.

AimThis research aims to guide future strategies for personalized treatment of primary mediastinal large B-cell lymphoma (PMBCL), particular … 53), CD58, beta-2-microglobulin (B2M), and exportin 1 (XPO1) genes; short tandem repeats at 6p21.3 [major histocompatibility complex (MHC) class I/II], 9p24.1 (PD-L1/PD-L2), 16p13.13 [class II, MHC, transactivator gene (CIITA)]), and cytogenetic profiles [myelocytomatosis oncogene (MYC)/8q24, B-cell lymphoma 2 (BCL2)/18q21, BCL6/3q27, del17p13, and karyotype abnormalities] were a …

Novel T cell receptor expression features in sperm and testis.

Except from the myeloid in origin cells, ectopic expression of T-cell receptors (TCRs) was also detected in sperm and the female reproductive tract, which in conjunction with major histocompatibility complex (MHC) molecules suggested their involvement in mate choice. Following-up these observations and considering that MHC/TCR interactions could guide spermatozoa towards ovum, the present study aimed to delineate the presence of TCRs in sperm vis-à-vis cognate recognition and define such expression during spermatogenesis. Immunofluorescence experiments using fertile BALB/c males showed that de…

Spontaneous Abortion and Myocardial Infarction: A Mendelian Randomization Investigation and Transcriptomic Analysis.

BACKGROUND: A link has been found between spontaneous abortion (SA) and myocardial infarction (MI). However, there is still a lack of compre … y. Furthermore, strong correlations were observed with various immunologic gene sets, including the Major Histocompatibility Complex (MHC), immunoactivators, and immunosuppressors. CONCLUSION: This study reveals a robust causal relationship between SA and MI, highlighting genetic and immunological pathways that could inform future research and therapeutic approaches.

Altered Protein Structures and Neoepitopes in Lupus Neutrophils From Dysregulated Splicing of Messenger RNA.

OBJECTIVE: To test whether messenger RNA (mRNA) splicing is altered in neutrophils from patients with systemic lupus erythematosus (SLE) and … these novel amino acid sequences were predicted to bind to the individual patients' class I and II major histocompatibility complex molecules with high affinity. CONCLUSION: We conclude that aberrant mRNA splicing in SLE has the potential to affect both the function of granulocytes and to generate novel autoantigens.

Recombinant human urinary trypsin inhibitor improves the immunological function of splenic dendritic cells in mice with acute lung injury.

AIM OF THE STUDY: Acute lung injury (ALI) is a common critical condition in the emergency department and is associated with a high mortality … ent with rhUTI could markedly upregulate the levels of co-stimulatory molecules (CD80 and CD86) and major histocompatibility complex class II molecules (MHC-II) on the surface of splenic DC and decreased the apoptosis rate of splenic DCs in LPS-induced ALI mice. In addition, protein levels of markers of endoplasmic reticulum stress (ERS) and ERS-related apoptotic pathways (includ …

Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates.

BACKGROUND: Long-term renal allograft acceptance has been achieved in macaques using a transient mixed hematopoetic chimerism protocol, but similar regimens have proven unsuccessful in heart allograft recipients unless a kidney transplant was performed simultaneously. Here, we test whether a modified protocol based on targeting CD154, CD2, and CD28 is sufficient to prolong heart allograft acceptance or promote the expansion of regulatory T cells. METHODS: Eight macaques underwent heterotopic allo-heart transplantation from major histocompatibility complex-mismatched donors. Induction treatmen…

Case Report: A novel CIITA mutation causing MHC class II deficiency: first reported case in Morocco.

Major histocompatibility complex class II (MHC II) deficiency (bare lymphocyte syndrome type II) is an autosomal-recessive combined immunodeficiency caused by pathogenic variants in the transcriptional regulators CIITA, RFXANK, RFX5, or RFXAP. While RFXANK founder mutations predominate in North Africa, CIITA-related disease is extremely rare. We report two siblings from a consanguineous Moroccan family with the classic early-infancy phenotype. The elder sister developed recurrent febrile rashes, oral candidiasis, and locoregional BCGitis with acid-fast bacilli in granulomas, followed by progre…

d) описательный обзор генетических и экологических факторов и риска множественного склероза. Разработка итальянского многоцентрического исследования PEDIGREE.

MS является результатом иммунопосредованного расстройства, вызванного экологическими факторами в генетически предрасположенных предметах. Педиатрические MS (Pediatric MS) представляют собой уникальное окно для изучения экологических факторов, поскольку пациенты близки к фактическому наступлению заболевания и подвергаются меньшему числу смешающих факторов. PedMS тесно связан с HLA-DRB1*15:01 и с вариантами, не связанными с MHC (основной комплекс анализа истолкования), с более высокой нагрузкой по сравнению со взрослыми. Похоже, аллея HLA-A*02 снижает риск MS. Роль редких вариантов все еще изуча

Совпадение в аннотации оригинала
MS is the result of an immune-mediated disorder triggered by environmental factors in subjects genetically predisposed. Pediatric MS (pedMS) … xposed to fewer confounding factors. PedMS is strongly associated to HLA-DRB1*15:01 and to non-MHC (Major Histocompatibility Complex) variants, with a higher burden compared to adults. HLA-A*02 allele seems to reduce MS risk. The role of rare variants is still under investigation. Several environmental causative factors have been identified: obesity, passive smoke, sun exposure, …

Рассечение вируса мюрин-энцефаломиелита Нейротропика Тейлера вызвало атрофию мозга у мышей первого класса C57BL/6 фона.

Атрофия мозга является общей особенностью нейродегенеративных расстройств, включая болезнь Альцгеймера, болезнь Паркинсона, множественный склероз и, в последнее время, инфекцию SARS-COV-2, в отношении которой неврологический механизм не полностью понятен. Тем не менее, нейроинфламмация и аккумулирование клеток CD8 Т часто наблюдается в посмертных мозговых тканях пациентов с нейродегенерацией. Поэтому мы разработали модель атрофии головного мозга с использованием модели инфекции вирусом мюрин энцефаломиелита (TMEV) нескольких склерозов. Для анализа вклада инфильтрации иммунных клеток и начала а

Совпадение в аннотации оригинала
Brain atrophy is a common feature of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, an … ler's murine encephalomyelitis virus (TMEV) infection model of multiple sclerosis. We employ single major histocompatibility complex (MHC) class I molecule conditional knockout mice generated by our program to analyze the contribution of immune cell infiltration and onset of atrophy. TMEV infected C57BL/6 mice that singularly express H-2Kb or H-2Db were evaluated. TMEV infection …

Enhancing the immunogenicity of Wilms tumor 1 epitope in mesothelioma cells with immunoproteasome inhibitors.

The immunogenicity of cancer cells is influenced by several factors, including the expression of the major histocompatibility complex class I (MHC-I), antigen expression, and the repertoire of proteasome-produced epitope peptides. The malignant pleural mesothelioma cell line ACC-MEOS-4 (MESO-4) expresses high levels of MHC-I and Wilms tumor 1 (WT1) tumor antigens. Using a functional T cell reporter assay specific for the HLA-A*24:02 restricted WT1 epitope (WT1235, CMTWNQMNL), we searched for factors that augmented the immunogenicity of MESO-4, focusing on proteasomes, which have a central role…

Effects of High Efficacy Multiple Sclerosis Disease Modifying Drugs on the Immune Synapse: A Systematic Review.

BACKGROUND: Co-signaling and adhesion molecules are important elements for creating immune synapses between T lymphocytes and antigen-presenting cells; they positively or negatively regulate the interaction between a T cell receptor with its cognate antigen, presented by the major histocompatibility complex. OBJECTIVES: We conducted a systematic review on the effects of High Efficacy Disease Modifying Drugs (HEDMDs) for Multiple Sclerosis (MS) on the co-signaling and adhesion molecules that form the immune synapse. METHODS: We searched EMBASE, MEDLINE, and other sources to identify clinical …

Immunoinformatics design and synthesis of a multi-epitope vaccine against Helicobacter pylori based on lipid nanoparticles.

Helicobacter pylori (H. pylori) is responsible for various chronic or acute diseases, such as stomach ulcers, dyspepsia, peptic ulcers, gast … proteins of H. pylori, namely, Urease, CagA, HopE, SabA, and BabA, were used. Immunogenicity, MHC (Major Histocompatibility Complex) bonding, allergenicity, toxicity, physicochemical analysis, and global population coverage of the entire epitopes and final construct were carefully examined. The study involved using various bioinformatic web tools to accomplish the following task …