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关键词： HIV   Gut   Innate immunity   CD4+T lymphocytes   type I interferon   T cell immune activation   TLR  

摘要： While much is known about the expression of interferon (IFN) pathways in the blood of people living with HIV (PLWH), their role in the intesinal tract has only recently been appreciated. The aim of this study was to evaluate gut mRNA expression levels of innate immune genes involved in the HIV-host interaction and their association with CD4+ T cell immune activation in long-term HAART-experienced PLWH. PLWH had increased intestinal levels of TLR4, type I IFN (IFN-alpha 2, IFN-alpha 14, IFN-beta) and IFNAR1 mRNAs, as well as increased frequencies of CD4+ T lymphocytes expressing CD38 or HLA-DR compared to the healthy donors. Moreover, TLR4, TLR9, IRF3, IRF7 and IFN-alpha 14 mRNA expression was positively correlated with the frequency of CD4+ T cells expressing CD38 or HLA-DR. These findings suggest a dysregulation of innate immunity, particularly of the TLRs and IFN pathways in the gut of PLWH. Genes in these pathways also appear to correlate with the levels of CD4+ T cell immune activation.

关键词： IL-15/IL-15R alpha   DHA   Adipocytes   Immune therapy   NK cell   CD8+T cell  

摘要： Malignant ascites (MA) presents a complex clinical challenge, linked inextricably to poor prognosis, chemoresistance, and metastasis of peritoneal carcinomatosis (PC). However, standard therapeutic approaches for managing or preventing MA secondary to PC remain unavailable. Here we display that a bioengineered adipocyte, encapsulating long-chain fatty acids and concurrently secreting IL-15 and IL-15 receptor alpha (IL-15R alpha), markedly extends the half-life and bioactivity of IL-15. The bioengineered adipocyte consists of an IL-15-P2A-IL15R alpha-T2A-mCherry cDNA sequence stable transfected 3T3-F442A preadipocyte cell line and dcosahexaenoic acid (DHA) are simultaneously encapsulated in the lipid droplets of mature adipocytes, which release it into the MA upon tumor cell-triggered lipolysis. We demonstrate that the bioengineered adipocytes led to specific expansion and activation of NK/CD8+ T cells response to the IL-15/IL-15R alpha complex in MA, thereby reversing immunosuppressive phenotype of ascitic immune cells and enabling them to recognize and attack cancer cells. This synergistic therapeutic strategy exhibits therapeutical manipulation of the ascitic immune cells, restores normal immune functioning, and suppresses cancer cell metastasis and tumor growth in ovarian cancer and colon cancer, all while minimizing systemic adverse effects.

关键词： Familial Mediterranean fever   Inflammation   IL18   M694V mutation   miRNAs  

摘要： ObjectivesFamilial Mediterranean fever (FMF) is a multifaceted autoimmune disease and requires a diligent strategical approach considering disease periods and mutation subtypes. We aimed to investigate serum levels of autoimmunity-related cell-free miRNAs and inflammatory and apoptotic markers in FMF *** FMF patients, of which 30 were in attack (FMF-A) and 30 were in remission (FMF-R) periods, and 25 age-, sex-, and BMI-matched healthy controls were included in our study. The expression levels of miR-26a-5p, miR-146a-5p, miR-155-2-5p, and miR-451a were analyzed with reverse-transcriptase quantitative polymerase chain reaction, and protein levels of interleukin-18 (IL18) and soluble Fas cell surface death receptor (sFAS) were measured with enzyme-linked immunosorbent assay. Serum CRP levels were analyzed by nephelometry, ferritin levels by chemiluminescence, and routine biochemical parameters by spectrophotometry. Correlation analyses were performed to seek potential associations of miRNAs with serum markers and biochemical parameters. Potential biomarkers were tested with receiver operating characteristic *** observed elevated serum IL18 levels but not sFAS, in FMF patients, particularly during attack period. IL18 demonstrated diagnostic value and was significantly correlated with acute-phase markers namely CRP, fibrinogen, and ferritin. Altered levels of IL18 and miR-451a could distinguish FMF patients in the attack period from the ones in remission. miR-26a-5p, miR-146a-5p, and miR-155-2-5p were downregulated in FMF patients carrying M694V *** findings suggest that IL18 and specific miRNAs can serve as potential biomarkers for FMF pathogenesis. Discovering promising targets for FMF-related miRNAs using mechanistic strategies will enhance our understanding of FMF disease management and *** Points center dot miR-451a and IL18 can serve as an indicator in distinguishing familial Mediterranean fever patie

关键词： HLA   next generation sequencing   novel allele  

摘要： We report here 56 novel HLA alleles identified in Hong Kong Chinese individuals. They have been submitted and officially named by the World Health Organization Nomenclature Committee for Factors of the HLA System in the year 2024.

关键词： APC   HLA haplotypes   NetMHCpan   SARS-CoV-2   T-cell immunity  

摘要： Infection with SARS-CoV-2 results in mild to severe COVID-19 disease courses. Several studies showed the association of impaired T-cell responses and certain HLA haplotypes with disease severity. However, it remained unclear if T-cell activation was compromised due to a general reduction of presented epitopes or other intrinsic factors within APCs or T cells. Furthermore, a potential reduction of presented epitopes would suggest if an upcoming SARS-CoV-2 variant could escape T-cell immunity. Hence, knowledge about the T-cell epitope landscape of SARS-CoV-2 would allow to better understand mechanisms leading to severe disease and to estimate the potential stability of the T-cell response in light of virus evolution, which might provide insights for future vaccine designs. Hence, in the present study, the T-cell epitope landscape of SARS-CoV-2 was determined via in vitro T-cell stimulation plus in silico prediction. HLAs associated with mild and severe disease courses showed almost the same potential in epitope presentation, suggesting intrinsic factors of APCs or T cells as contributors to the more severe disease courses. As T-cell epitopes did also not originate from regions of SARS-CoV-2 having shown high mutation rates in the past, a relatively stable T-cell response can be expected regarding new SARS-CoV-2 strains in the future. Analysis of the T-cell epitope landscape of SARS-CoV-2 suggests T-cell intrinsic factors as likely modulators of disease severity and that the capacity of MHC-peptide presentation remains stable among circulating SARS-CoV-2 viral strains.

关键词： Follow-up   Heart failure   Risk stratification  

摘要： Heart failure is a syndrome with a high clinical and healthcare impact. Currently, the incidence in Europe is approximately 5/1000 people/year in the adult population, with a prevalence of 1-2%. The prognosis is burdened by a still high mortality and hospitalization rate. The phase immediately following the hospitalization is defined as the "vulnerable period" because it is characterized by the greatest number of clinical events: 30% risk of rehospitalization and 10% risk of death. Taking care of the patients in this phase is crucial and must be accompanied by a risk stratification process, essential for planning a follow-up that is as personalized as possible, also necessary for resource optimization. In the chronic phase of the disease, risk stratification appears similarly important, as it could represent a support tool in the patient's transition from hospital to the community. The aims of this paper are to review the recommendations for the follow-up of the European and American guidelines, describe the tools available to the clinician to stratify the prognosis and diversify the pathway, and finally hypothesize a follow-up scheme both in the post-acute and chronic phases.

关键词： chronic periapical lesions   cytokine expression   diode laser   interleukin 8   intracanal irradiation   retreatment  

摘要： This clinical study assessed the effectiveness of diode laser-980 nm as adjuvant in retreatment of failed endodontic cases with chronic periapical lesions on basis of IL-8 expression and postoperative pain when compared to placebo. For 28 patients, the pre-instrumentation periapical samples (S1) were gathered, following retreatment. After chemo-mechanical preparation, post-instrumentation samples (S2) were collected. Patients were allocated to diode laser (DL) or placebo (PL) groups. After which post-irradiation samples (S3) were gathered. Patients recorded their pain on NRS scale at 6, 12, 24 and 7 days. After 1 week, samples (S4) were collected. An ELISA kit was used to measure an amount of IL-8. DL group showed significantly lower IL-8 levels at S4 (p < 0.001) and postoperative pain at 6 h (p = 0.003) compared to PL. Intracanal diode laser irradiation is a beneficial adjunct to endodontics, in retreatment cases regarding reducing postoperative pain and lowering the level of IL-8 expression.

关键词： DPB1*1762:01   HLA novel alleles   HLA-DP  

摘要： Description of the novel HLA-DPB1*1762:01 allele.

关键词： T(H)9 cells   IL-9 expression   human CD4(+) T-cell differen-tiation   cytokines   inborn errors of immunity  

摘要： Background: CD4+ T cells play essential roles in adaptive immunity. Distinct CD4+ T-cell subsets-TH1, TH2, TH17, TH22, T follicular helper, and regulatory T cells-have been identified, and their contributions to host defense and immune regulation are increasingly well defined. IL-9-producing TH9 cells were described in 2008 and appear to play both protective and pathogenic roles in human immunity. However, key requirements for generating human TH9 cells remain incompletely defined. Objective: We sought to define signaling pathways that regulate IL-9 production by human CD4+ T cells. Methods: Human naive and memory CD4+ T cells were cultured under different conditions, and the molecular mechanisms regulating IL-9 induction were determined by assessing the ability of CD4+ T cells from a broad range of patients (n = 92) with pathogenic variants in key immune genes (n = 21) to differentiate into IL-9+ cells. Results: We identified 2 culture conditions that yielded IL-9-expressing cells from naive CD4+ T cells and amplified IL-9 production by in vivo-generated memory CD4+ T cells: TGF-(3 plus IL-4 (ie, TH9 polarizing condition), and the combination of IL-21, IL-23, IL-6, IL-1(3, and TGF-(3 (ie, TH17 polarizing condition). Combining these conditions had a synergistic effect in generating IL-9+CD4+ T cells. IL-9 induction required STAT3-activating cytokines as well as intact signaling via the T-cell receptor and STAT5. Importantly, IL-9 induction was restrained by IFN-y/STAT1 and IL-10. Conclusions: Our findings revealed critical molecules involved in inducing/restraining IL-9 production by human CD4+ T cells, thereby identifying pathways that could be targeted to modulate IL-9 in health and disease.