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关键词： CD8+T cells   HLA-B*18:01   influenza B virus   molecular dynamics   X-ray crystallography  

摘要： The influenza B virus (IBV) can pose a significant threat to global health. Despite this, IBV is under studied compared with influenza A virus (IAV). CD8+ T cells have proven highly effective in reducing influenza diseasese verity. In addition, pre-existing immune responses towards IAV epitopes may provide protection against homologous IBV-derived peptides due to T cell cross-reactivity. To exploit the advantages of T cells for future vaccine developments, a better understanding of the IBV-derived peptide presentation by the highlypolymorphic human leukocyte antigen (HLA) is required. We previously determined that the IAV-derivedPB1177-A peptide was presented by the HLA-B*18:01 molecule and induced CD8+ T cell responses. Here, weassessed the PB1177-A IBV homologue (PB1177-B). Intracellular cytokine staining assays showed that PB1177-Bwas unable to activate CD8+ T cells from several HLA-B*18:01+ samples tested. We determined that the IAV-and IBV-derived PB1177 adopted different stability and conformation in the cleft of HLA-B*18:01. Moleculardynamics analysis on the crystal structure showed that PB1177-B had a central flexible region with a largehydrophobic patch formed by two phenylalanine residues, not present in PB1177-A. The flexibility and the lower stability of the HLA-B*18:01-PB1177-B complex may hinder CD8+ T cell receptor binding, under pinning the lack of CD8+ T cell activation observed. This provides additional insights into the differences between IAV-and IBV-specific CD8+ T cell responses.

关键词： Amygdalin   Cartilage defects   Fibrocartilage   Interleukin-17A   Magnesium  

摘要： Background/objective: Cartilage defects (CDs) present a significant challenge in orthopaedic medicine. Owing to the inherently limited regenerative capacity of cartilaginous tissue, defects usually do not heal via natural repair processes. Consequently, damaged tissue is replaced by fibrocartilage-like tissues instead of the original hyaline cartilage. Therefore, inhibiting fibrocartilage formation while promoting hyalinisation may represent a novel strategy for CD therapy. Although studies have explored the role of interleukin (IL)-17A and ferroptosis in the fibrosis of visceral organs, such as the liver, lungs, and kidneys, their implication in cartilage fibrosis and fibrocartilage formation remains unclear. Herein, we aimed to determine whether IL-17A and ferroptosis are collectively involved in the process of cartilage fibrosis and to investigate the effects of amygdalin (AMD) and magnesium ions (Mg2+) in cartilage regeneration and the potential molecular mechanisms underlying these effects. Methods: Cartilage samples were collected from patients with osteoarthritis and subjected to immunohistochemistry analysis to assess fibrocartilage formation indicators within the degenerated areas. Quantitative realtime polymerase chain reaction, western blot, and immunohistochemistry analyses were employed to assess changes in cartilage anabolism and expression of fibrocartilage markers after treatment with different concentrations of AMD. We also treated chondrocytes with an IL-17A/RA antagonist, a ferroptosis inhibitor, a ferroptosis inducer, and AMD, and measured the changes in fibrocartilage-, ferroptosis-, and IL-17 signalling-associated factors. Finally, mice with microfracture (MF)-induced CDs were administered intra-articular injections of either saline, AMD (10 mu mol/L), MgCl2 (0.5 mmol/L), or AMD (10 mu mol/mL) plus MgCl2 (0.5 mmol/L) twice a week. After 4 and 8 weeks, chondral repair was assessed through histological and immunohistochemical analyses in each gro

关键词： MHC   HLA alleles   Mexican population   Disease associations   Systematic review  

摘要： Background. The major histocompatibility complex (MHC) plays a crucial role in immune responses and is associated with disease susceptibility. This study systematically reviews MHC class I and class II allele frequencies and their associations with diseases in the Mexican population from 1979 to 2023. Methods. A systematic review following PRISMA guidelines was conducted. Reports were obtained from the Allele Frequency Net Database and PubMed using keywords related to HLA and Mexican populations. A total of 776 reports were screened, and 214 were retained for final analysis. Seventy-six studies comprising allele frequency data from over 20,000 individuals across Mexican states and indigenous communities were analyzed. In addition, over 138 articles were examined to identify alleles associated with various diseases. Results. The analysis identified 117 alleles whose frequencies varied regionally within Mexico. While DPA1*01, DPB1*04:01, and DQA1*03 were predominant, DRB1*04, DQB1*03, and DQA1*05 were also prominent but variable. Certain alleles, such as A*02, B*35, C*04, and C*07, were relatively common in the population. Numerous disease correlations were uncovered, such as B*27's strong association with spondyloarthropathies. DRB1*15:01 and DRB1*04 conferred an increase in multiple sclerosis, while DRB1*04 may protect against some skin diseases. Conclusion. This review improves the understanding of MHC allele frequencies and disease associations in Mexicans, highlighting genetic diversity. The findings lay the groundwork for future research on genetic predispositions and health outcomes, aiding healthcare strategies in this diverse population. Further studies are needed to address data gaps and refine genetic profiles for targeted medical applications. (c) 2025 The Author(s). Published by Elsevier Inc. on behalf of Instituto Mexicano del Seguro Social (IMSS). This is an open access article under the CC BY license (http://***/licenses/by/4.0/)

关键词： Apoptosis   Autophagy   Caspases   Cancerous colorectal epithelia   IL-17a   Mucinosis  

摘要： Background/Aims. IL17-producing Th17 represent a distinct subset of T-cells. The link between IL-17a and the colorectal cancer (CRC) microenvironment has been widely accepted. However, the role of IL-17a in epithelial cell apoptosis, autophagy, mucinosis, ultrastructural changes, and their potential correlations with CRC remains unclear. Materials and Methods. Out of 2890 patients with CRC, 200 were divided into four groups (stage I-IV) and 50 into non-CRC/healthy/control. We investigated the relationship between IL-17a, apoptosis, autophagy, and mucinosis in patients with stage I-IV CRC ( in vitro/vivo). In addition to many (para)clinical assessments, IL-17a load in blood and the tumor microenvironment (TME) in patients with CRC were assessed. To examine these associations, the effect of IL-17a on CRC cells was evaluated using qPCR, Western blotting, ELISA, bioluminescence, flow cytometry, and immunohistochemistry (IHC), and ultrastructural changes in the colonic epithelia were assessed by scanning and transmission electron microscopy. Results. IL-17a is overexpressed in stage I-IV in the TME and in stage III-IV in the blood of patients with CRC. IL-17a upregulated apoptosis (caspases, cytochrome c (CYC), higher Bax:Bcl2 ratio), autophagy (SIRT1 and LC3), and the cell cycle (TP53, APC-1) and downregulated B3GALNT2 and mucins and led to morphological and nuclear changes in CRC epithelia. Conclusions. IL-17a is abundantly expressed in the CRC microenvironment, and IL-17aIL-17aR interactions play a critical role in the control of apoptosis and mucinosis. The observed remarkable association of IL-17a and apoptosis in adenocarcinoma provides valuable insight into the clinical implications of Th17/IL-17 in CRC. (c) 2025 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： cell metabolism   cell therapy   dendritic cells   IL-10   T regulatory cells   tolerance   tolerogenic DC  

摘要： Dendritic cells (DC) are professional antigen-presenting cells involved in promoting and controlling immune responses. Different subsets of DC, named tolerogenic (tol)DC, play a critical role in the maintenance of tissue homeostasis and in fostering tolerance. These unique skills make tolDC especially attractive for strategies aimed at re-establishing/inducing tolerance in immune-mediated conditions. The generation of potent tolDC in vitro from peripheral blood monocytes has seen remarkable advancements. TolDC modulate T cell dynamics by favoring regulatory T cells (Tregs) and curbing effector/pathogenic T cells. Among the several methods developed for in vitro tolDC generation, IL-10 conditioning has been proven to be the most efficient, as IL-10-modulated tolDC were demonstrated to promote Tregs with the strongest suppressive activities. Investigating the molecular, metabolic, and functional profiles of tolDC uncovers essential pathways that facilitate their immunoregulatory functions. This Review provides an overview of current knowledge on the role of tolDC in health and disease, focusing on IL-10 production, functional characterization of in vitro generated tolDC, molecular and metabolic changes occurring in tolDC induced by tolerogenic agents, clinical applications of tolDC-based therapy, and finally new perspectives in the generation of effective tolDC.

关键词： Alloantibody   Human Leukocyte Antigen   Histocompatibility  

摘要： HLA-DQ mismatch has been correlated with worse kidney allograft outcomes. However, there is linkage disequilibrium between HLA-DQ and HLA-DR, and the independent effect of HLA-DQ mismatches, particularly HLA-DQ alpha(3 heterodimer mismatches, on allograft outcomes after adjustment for HLA-DR mismatches has been understudied. It is also unknown whether the potential for HLA-DQ molecules to form cis- or trans-heterodimers impacts allograft outcomes. We analyzed 866 well-characterized kidney transplant recipients for the relevance of potential cis/trans-HLA-DQa(3 heterodimers on T cell-mediated rejection, antibody-mediated rejection, deathcensored allograft survival, and all-cause allograft survival. We found that including potential HLA-DQa(3 cis/ trans-heterodimer mismatches did not improve prediction models for all outcomes compared to HLA-DQa(3 cisheterodimers alone. We also studied the independent effect of HLA-DQa(3 mismatch on these outcomes after adjusting for HLA-DR mismatch in multivariate models. Both HLA-DR antigen and HLA-DQa(3 cis-heterodimer mismatch were univariate but not multivariate correlates of these outcomes when adjusted for each other. Collinearity between HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles, and the dilution of survival outcomes with non-alloimmune related events are potential reasons. This underlies the need for novel approaches to precision in alloimmune risk assessment, e.g., molecular mismatch, for use in prediction models and allocation algorithms.

关键词： HLA   HLA-C*07:1187   novel allele   sequencing-based typing  

摘要： HLA-C*07:1187 differs from HLA-C*07:02:01:01 by one nucleotide substitution in codon 304 in exon 5.

关键词： biologic therapy   dual biologic therapy   dupilumab   atopic dermatitis   psoriasis   psoriatic arthritis   inflammatory bowel disease   rheumatoid arthritis   TNF-alpha inhibitors