Immunologic Research最新文献

Baicalein, one of the major active flavonoids found in Scutellaria baicalensis, has been revealed to exhibit potent anti-inflammatory properties in allergic airway inflammation. This study aimed to explore the role of baicalein and its relevant mechanism in the treatment of allergic rhinitis (AR). The bioinformatics tools were used to predict the targets of baicalein and AR-related genes. AR mice were induced by ovalbumin (OVA) and treated with lentivirus-encapsulated knockdown of nuclear receptor subfamily 4 group A member 1 (NR4A1) or protein arginine N-methyltransferase 1 (PRMT1) plasmids and baicalein. IL-4/IL-13-induced human nasal mucosal epithelial cells (HNEpC) were transfected with knockdown of NR4A1 or PRMT1 plasmids and baicalein treatment. Baicalein alleviated AR-like symptoms and reduced the levels of immunoglobulin E, histamine, and LTC4 in serum and IL-4, IL-25, and IL-33 concentrations in nasal lavage fluids of mice induced with OVA by increasing NR4A1 expression. NR4A1 blocked the NFκB/p65 pathway by mediating transcriptional repression of PRMT1. Knockdown of PRMT1 overturned the effects of NR4A1 knockdown on IL-4/IL-13-induced HNEpC and OVA-induced mice. Collectively, these findings provide evidence that baicalein activation of NR4A1 mediates transcriptional repression of PRMT1 and relieves AR in mice by blocking the NFκB/p65 pathway.

The ABCC subfamily contains thirteen members. Nine of these transporters are called multidrug resistance proteins (MRPs). The MRPs have been associated with developing ulcerative colitis (UC). This study aimed to evaluate the ABCC expression in UC patients and its role in a dextran sulfate sodium (DSS)-induced colitis mice model under 5-aminosalicylates or methylprednisolone treatment and compared with control without inflammation. DSS-induced colitis mice were treated with 5-aminosalicylates (50 mg/kg 24 h) or methylprednisolone (2 mg/kg 24 h). Human rectal biopsies were obtained from UC patients. The abcc-relative mRNA levels and protein expression were determined by RT-PCR and immunohistochemistry. abcc4, abcc5, and abcc6 mRNA levels were significantly increased in DSS-induced colitis compared to the other groups. The 5-aminosalicylate treatment dramatically increased the abcc2 and abcc3 mRNA levels vs. control. Methylprednisolone treatment increased abcc1 vs. DSS-induced colitis and colitis treated with 5-aminosalicylate. Immunohistochemical analysis revealed down-regulation of ABCC1/ABCC2/ABCC5/ABCC7 in mice colitis vs. control. Treatment with 5-aminosalicylate restored ABCC5 levels, while methylprednisolone restored ABCC2/ABCC5/ABCC7 in colitis mice at similar control levels. Relative mRNA levels of mrp1-5 were increased in active UC patients vs. control. ABCC2/ABCC4/ABCC7 were conspicuously expressed in the mucosa of 5-aminosalicylate and/or methylprednisolone-treated UC patients, while ABCC2/ABCC4/ABCC5/ABCC7 in submucosa, ABCC1/ABCC5/ABCC7 in muscular, and ABCC1/ABCC4/ABCC5/ABCC7 in serosa were expressed vs. controls. This is the first report about the differential up-regulation of the ABCC subfamily gene and protein expression in DSS-induced colitis under aminosalicylates or methylprednisolone treatment.

Mitophagy, the selective degradation of mitochondria by autophagy, plays a crucial role in cancer progression and therapy response. This study aims to elucidate the role of mitophagy-related genes (MRGs) in cutaneous melanoma (CM) through single-cell RNA sequencing (scRNA-seq) and machine learning approaches, ultimately developing a predictive model for patient prognosis. The scRNA-seq data, bulk transcriptomic data, and clinical data of CM were obtained from publicly available databases. The single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were used to identify gene modules associated with mitophagy phenotypes. A machine learning framework employing ten different algorithms was used to develop the prognostic model. Based on scRNA-seq data, we identified 16 distinct cell subpopulations in melanoma, and melanoma cells exhibited significantly higher mitophagy scores. The turquoise module identified via WGCNA showed the strongest correlation with mitophagy scores. A prognostic model incorporating seven genes was developed through machine learning algorithms, achieving an average C-index of 0.754 across training and validation cohorts. Functionally, low-risk patients were enriched in interferon-gamma response and inflammatory processes, whereas high-risk patients showed enrichment in glycolysis regulation and signaling pathways such as KRAS and Wnt/β-catenin. Notably, low-risk patients demonstrated enhanced immune infiltration and greater sensitivity to immunotherapy. RT-qPCR validated the expression level of 7 model genes in human melanoma cell lines and normal melanocyte cell lines. Our study provides a comprehensive understanding of MRGs in melanoma and presents a novel prognostic model. These findings enhance our understanding of the tumor microenvironment and may guide personalized treatment strategies for CM patients.

Congenital neutropenia (CoN) is a heterogeneous group of inborn errors of immunity (IEI) characterized by recurrent infections and early onset of neutropenia (NP). This study aimed to investigate the demographic and clinical data of children with CoN and idiopathic neutropenia (IN) in Morocco. We performed a retrospective study of patients with CoN and analyzed the clinical and laboratory findings of patients with CoN and IN diagnosed between 1999 and 2018 in a clinical immunology unit of a large pediatric hospital. We identified 88 patients, 51 with IN and 37 with CoN. Fifty-seven percent were males, and 43% were females, ranging from 1 month to 19 years. The median age at onset was 8 months, and the median at diagnosis was 36 months. Consanguinity was observed in 57% of the cases, and a history of recurrent infections in the siblings was found in 27.3%. The most common infectious complications were ear, nose, and throat (ENT) infections, skin and soft tissue infections, and lung infections. Patients with CoN were classified into seven syndromes: 9 with severe congenital neutropenia, 11 with cyclic neutropenia, 6 with glycogen storage disease type 1b, 5 with poikiloderma with neutropenia, 3 with Griscelli syndrome, 2 with Hermansky-Pudlak syndrome type II, and 1 with Cohen syndrome. This study provides a comprehensive overview of CoN and IN in a pediatric cohort from Morocco, representing the country's most considerable single-center investigation of these conditions. Our findings highlight the significant burden of CoN, accounting for 5% of IEI in the Moroccan registry, a proportion higher than in some neighboring countries. The study emphasizes the early onset and severity of bacterial infections in CoN patients, underlining the critical need for timely and accurate diagnosis.

Psoriasis is a chronic, immune-mediated disease. The systemic inflammation triggered by psoriasis contributes significantly to increased cardiovascular risk. While various treatments completely clear the skin, the associated effects on systemic inflammation are not yet clear. We investigated residual systemic inflammation in successfully treated patients. Circulating disease-specific and non-specific inflammatory markers were measured and compared in 80 psoriasis patients (aged 30-45 years) successfully treated with topical therapy, methotrexate, adalimumab, secukinumab or guselkumab, and in 20 healthy controls. Non-specific inflammatory markers (high-sensitivity C-reactive protein (hs-CRP), complete blood count (CBC) parameters, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume-to-platelet ratio (MPR), and red blood cell distribution width-to-platelet ratio (RPR)) and disease-specific inflammatory markers (interferon-γ (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-1β, IL-12p70, IL-17, and IL-23) were measured and compared between groups. Disease-specific cytokines (IFN-γ, TNF, IL-1β, IL-12p70, and IL-17, but not IL-23), were significantly elevated in patients compared to controls, while non-specific inflammatory markers showed no differences compared to controls. The residual disease-specific cytokines were similarly elevated in all five treated groups. In addition, they correlated significantly with body mass index (BMI) and waist circumference. Our results suggest that psoriasis patients have elevated residual disease-specific cytokines despite successful treatment, while the non-specific inflammatory markers are similar to those in control subjects. Residual disease-specific inflammatory markers correlated with BMI and waist circumference. A possible beneficial effect of body weight control in psoriasis patients merits further investigation. The study was registered at http://clinicaltrials.gov (identifier: NCT05957120) on July 24, 2023.

Chronic muscle fatigue is a condition characterized by debilitating muscle weakness and pain. Based on our recent finding to study the potential effect of mTOR on ATG13 inactivation in chronic muscle fatigue, we report that biweekly oral administration with MHY1485, a potent inducer of mTOR, develops chronic illness in mice resulting in severe muscle weakness. As a mechanism, we observed that MHY1485 feeding impaired ATG13-dependent autophagy, caused the infiltration of inflammatory M1 macrophages (Mφ), upregulated IL6 and RANTES by STAT3 activation, and augmented demyelination in muscle-serving nerve fibers. Interestingly, these mice displayed worsened muscle fatigue during 2-day post-treadmill exercise, suggesting the critical role of chronic mTOR activation in potential PEM pathogenesis. Interestingly, ATG13-repressor mice exhibited enhanced infiltration of M1Mφ cells, STAT3 activation, demyelination of nerve fibers, and PEM-like symptoms, suggesting the potential role of ATG13 impairment in post-exertional fatigue. HIGHLIGHTS: The potential role of mTOR activation in post-exertional fatigue is highlighted. As a molecular mechanism, mTOR activation augments autophagy impairment via ATG13 inactivation. Autophagy impairment induces IL-6 and RANTES via STAT3, demyelinates nerves in the muscle and spinal cord. ATG13 repressor mice (Tg-ATG13) displayed inflammatory demyelination and post-treadmill fatigue.

A systematic review and meta-analysis were performed to evaluate the virus-specific T-cell response after COVID-19 mRNA vaccination, using the QuantiFERON SARS-CoV-2 interferon-γ release assay. A search was conducted (June 8, 2023) in the PUBMED, SCOPUS, and medRxiv databases, to identify studies reporting the QuantiFERON SARS-CoV-2 (Starter (two antigen tubes) or Starter + Extended Pack (three antigen tubes), cut-off ≥ 0.15 IU/mL) positivity rate (PR) in immunocompetent adults, following the administration of two or three COVID-19 mRNA vaccine doses. Study quality was evaluated with the Critical Appraisal Skills Programme Tool. A meta-analysis was conducted using a random-effects model. Heterogeneity and publication bias were assessed. Eleven eligible studies (with 5-73 vaccinated immunocompetent participants) were identified. For COVID-19-naïve participants, ≤ 3 months after the second dose, the pooled PR (random-effects model) was 86 (95% confidence interval (95% CI) 78-95%). Comparing the Starter vs. the Starter + Extended Pack, a significant difference in PRs was detected (80.6% vs. 100% p-value < 0.001). At 3-6 and >6 months after the second dose and ≥ 3 months after the third dose, the pooled PRs were 59% (95% CI 45-72%), 79% (95% CI 66-92%), and 66% (95% CI 50-82%), respectively. For convalescent participants, ≥ 6 months after the third dose, the pooled PR was 81% (95% CI 67-95%). Limitations include heterogeneity and a small number of studies, at some timepoints. In conclusion, following the second or third COVID-19 mRNA vaccine dose, QuantiFERON SARS-CoV-2 detected positive responses in a certain percentage of the vaccinees, possibly because of waning immunity, reduced assay sensitivity, or lack of T-cell response induction in some vaccinees. The detection of positive responses was higher when the Starter + Extended Pack was used. PROSPERO Registration Number: CRD42023431315.

This study aims to characterize the majority of immune cell subsets in peripheral blood mononuclear cells in children with Mycoplasma pneumoniae pneumonia (MPP) by a 21-color flow cytometry panel. Patients who met the predetermined eligibility criteria for pneumonia diagnosis were recruited for the research study. Multi-color flow cytometry was conducted on the peripheral blood mononuclear cells of each patient group, which were then subjected to dimensionality reduction and cluster analysis. In our study, the proportion of activated CD4 + T cell and naïve CD8 + T in children with MPP was higher than that of children with non-MPP, and the proportion of CD8 + T cell and central memory CD8 + T cell in MPP children was lower. Central memory CD4 + T cell and activated CD4 + T cell in the severe MPP were higher than those in the mild MPP. The highest proportions of CD8 + T cell, CD8 + Tn cell, activated CD8 + T cell, and total activated T cell were observed in the pulmonary consolidation-mucous group when compared to the pulmonary consolidation-necrosis and bronchiolitis groups. In the pulmonary consolidation-necrosis group, the proportions of central memory CD4 + T cell and T helper 17 cell were higher than those in pulmonary consolidation-mucous and bronchiolitis groups. In the bronchiolitis group, the percentages of CD4 + T cell, naïve CD4 + T cell, and T helper 2 cell were higher than those in pulmonary consolidation-mucous and the pulmonary consolidation-necrosis groups. The T lymphocyte subsets were different among various groups, offering new insights into the immune system of pediatric patients with Mycoplasma pneumoniae pneumonia.

Helicobacter pylori (Hp) has been postulated as an infectious trigger of psoriatic disease, namely psoriasis (Ps) and psoriatic arthritis (PsA), but meticulous antibody (ab) reactivity against all dominant and subdominant Hp antigens in demographically matched PsA and Ps patients and healthy controls has not been performed so far. IgG anti-Hp ab testing was performed by combining immunoblotting and line assays in 263 serum samples from 89 patients with PsA, 114 patients with Ps, and 60 demographically matched healthy controls (HCs). Anti-Hp positivity did not differ between PsA, Ps, and HCs (P > 0.05 for all comparisons). In PsA, anti-p75, anti-p67-FSH, anti-p66-UreB, anti-p54-flagellin, anti-p41, and anti-p30-OMP abs were more frequent in patients compared to HCs (P < 0.001, P = 0.028, P = 0.010, P = 0.003, P = 0.012, P = 0.020 respectively). In Ps, anti-p66-UreB and anti-p54-flagellin abs were more frequent than HC (P = 0.015 and P = 0.011, respectively), while anti-p50 abs were less frequent than HCs (P = 0.008). Anti-p75, anti-p67-FSH, anti-p50, anti-p41, anti-p30-OMP, anti-p29 = UreA and anti-p26 ab levels were higher in PsA compared to Ps (P = 0.012, P = 0.036, P < 0.001, P = 0.021, P = 0.002, P = 0.006 and P = 0.021 respectively). DAS28 scores were positively correlated with anti-p19 ab levels (r = 0.349, P = 0.050) in PsA patients by linear regression analysis. No other significant clinical association with anti-Hp responses was noted in patients with PsA and Ps. Our results demonstrate that several antigen-specific anti-Hp abs are more frequent in patients with psoriatic disease; however, negative correlations also exist, raising doubts about whether Hp is immunologically linked to psoriatic disease.