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摘要： INTRODUCTION:Antibody-mediated rejection (AMR) is one of the major obstacles to successful kidney transplantation. The T helper cell subset that plays a key role in the activation of B-lymphocytes and antibody production is T follicular helper (Tfh) cell. Therefore, we aimed to compare the percentage of Tfh cells and the serum level of interleukin 21 (IL-21), mainly secreted by this subset, in patients with AMR and stable recipients. METHODS:Peripheral blood samples were taken from 30 patients diagnosed with AMR and 30 stable kidney transplant recipients as well as 10 age- and sex-matched healthy individuals. The percentage of circulating Tfh cells (TCD4+CXCR5+PD1+) and the level of IL-21 were studied by flow cytometry and ELISA techniques, respectively.  Results. The proportion of cTfh cells among circulating TCD4+ cells in AMR patients was markedly elevated compared to the other groups (P < .0001). It was also higher in stable recipients than in healthy controls (P < .0001). The serum level of IL-21 was increased in AMR patients compared to stable recipients (P = .03) and healthy participants (P = .02). In addition, there was a significant negative correlation between cTfh percentage and the estimated glomerular filtration rate (eGFR) in transplanted patients (P = .001). Moreover, the AUC of cTfh cells in AMR diagnosis was 0.83 [95% CI 0.73-0.93 (P < .0001)]. CONCLUSION:In AMR patients, cTfh cell percentage and IL-21 levels were significantly increased. The significant association between cTfh % and eGFR, with an AUC of 0.83, indicates its potential as a diagnostic and prognostic marker in AMR.

关键词： IL-22   Predictive biomarker   Radiation   Intestinal injury   Radiosensitivity  

摘要： Considering the beneficial role played by IL-22 in alleviating radiation-induced intestinal injury through its promotion of epithelial regeneration, it was hypothesized that individuals with elevated IL-22 levels might display either minimal intestinal injury or increased resistance following ionizing irradiation exposure. To assess the impact of IL-22 on intestinal radiosensitivity, IL-22 expression levels was detected in serum of normal mice. Mice naturally with high or low levels of IL-22 or pretreated with IL-22 or anti-IL-22 were subjected to 10 Gy of total abdominal radiation (TAI). Daily observation, morphometric analysis, quantitative reverse transcriptase polymerase chain reaction, immunohistochemistry and western blot were employed to measure weight loss, survival rate, cell proliferation and death, and DNA damage. Furthermore, influence of IL-22 pretreatment on survival of intestinal organoid exposed to 6 Gy X-rays was evaluated. The results showed that IL-22 expression levels were varied between individuals. Surprisingly, mice with high IL-22 levels displayed exacerbated intestinal injury manifesting as increased weight loss, reduced regeneration capacity and more cell apoptosis. Notably, a strong positive correlation between weight loss and IL-22 expression level was observed. Additionally, pretreatment with IL-22 resulted in increased mortality accompanied by enhanced cell apoptosis and DNA damage in crypt of early exposure, as well as diminished survival of intestinal organoid, while pretreatment with anti-IL22 antibody alleviated the intestinal injury. In this study, we established a direct link between IL-22 and radiosensitivity, suggesting IL-22 could be used as a potential biomarker for predicting individual intestinal radiosensitivity prior to radiation exposure.

关键词： Mycobacterium genavense   nAIGA   IL-2   IFN-gamma   Lymphadenitis  

摘要： BackgroundInfections with atypical mycobacteria are rare and sometimes difficult to correctly diagnose. In many cases underlying diseases such immune deficiency can promote these *** presentationA 43-year-old male of Southeast Asian origin presented to our tertiary care hospital with persistent cervical lymphadenopathy non-responsive to antibiotics. Imaging suggested malignancy, but a biopsy did not confirm this suspicion. PCR diagnostics identified Mycobacterium genavense and further immunological testing revealed an acquired adult-onset immunodeficiency due to neutralizing anti-IFN-gamma autoantibodies (nAIGA), explaining both the current infection and previous pleural empyema. The patient responded well to triple antimycobacterial therapy, with no recurrence or novel infection after almost two *** case highlights the importance of considering underlying immunodeficiencies and the patient's geographic origin in the diagnosis of rare infections.

关键词： 胸腺肿瘤   B3型胸腺瘤   胸腺癌   CD5阳性，CD117阳性，TdT  

摘要： 目的 探讨伴CD5和（或）CD117阳性及缺乏TdT阳性淋巴细胞的纵隔B3型胸腺瘤临床病理学特征。方法 收集广东医科大学附属医院病理科2023年12月至2024年7月明确诊断的2例伴CD5和（或）CD117阳性及缺乏TdT阳性淋巴细胞的纵隔B3型胸腺瘤，结合文献复习，分析总结其临床病理学特征。结果 2例患者均为男性，年龄分别为54岁、73岁，均无明显呼吸系统临床症状，无吸烟史，均为前纵隔占位，肿瘤直径分别为53mm、72mm，镜下肿瘤细胞均呈B3型胸腺瘤样形态，免疫组化显示CD5和（或）CD117阳性表达，并缺乏TdT阳性的淋巴细胞；均点灶表达MUC1、部分表达GLUT1；例1患者行根治性手术切除，术后行局部放疗，随访至今13个月无瘤生存，例2患者明确诊断时已伴胸膜、肝脏转移，拒绝进一步放化疗，随访2个月肿瘤进展后失访。结论 伴CD5和（或）CD117阳性及缺乏TdT阳性淋巴细胞的纵隔B3型胸腺瘤罕见，好发于男性、前纵隔，结合形态学及免疫组织化学联合CD5、CD117、TdT、MUC1、GLUT1有助于鉴别胸腺癌。该肿瘤生物学行为及生存趋势可能介于B3型胸腺瘤与胸腺癌之间，相关研究报道甚少，仍有待积累更多的病例进一步深入研究与分析。

关键词： IL-27   Diabetic wound healing   Macrophage   M1-to-M2 polarization   STAT3  

摘要： Diabetic foot ulcer (DFU), a serious complication of diabetes, is a life-threatening disease that often leads to lower limb amputation and a shortened lifespan. Interleukin-27 (IL-27) is a member of the IL-12 family and has the potential to exert dual effects on the immune response. The role of IL-27 in diabetic skin wound healing is unknown. The aim of this study was to investigate whether there is abnormal expression of IL-27 in diabetic skin and whether supplementation with IL-27 can promote diabetic wound healing by modulating macrophage polarization. We established a streptozotocin (STZ)-induced diabetic mouse model and constructed diabetic wounds. We assessed protein expression by western blotting (WB) and immunohistochemical (IHC) staining. We also performed hematoxylin-eosin (H&E) staining and Masson's trichrome staining. In the presence of lipopolysaccharide (LPS) and high glucose (HG), we treated the mononuclear macrophage line RAW264.7 and bone marrow-derived macrophages (BMDMs) with IL-27. To assess macrophage polarization, we examined the expression of inducible nitric oxide synthase (iNOS), IL-1 beta and arginase-1 (Arg-1). To understand the underlying mechanisms, we used macrophage IL-27ra knockout mice to knockout macrophage IL-27 receptors. Our in vivo experiments revealed that the expression of IL-27 in the skin of diabetic mice was significantly decreased and that supplementation with IL-27 promoted diabetic wound healing. In vitro, compared with the LPS group, supplementation with IL-27 alleviated the suppression of multiple cellular functions, such as iNOS and IL-1 beta expression, cell migration, and phagocytosis, in macrophages after HG exposure. Mechanistically, we found that IL-27 expression was decreased and that the activation of signal transducer and activator of transcription 3 (STAT3) by phosphorylation was inhibited in diabetic skin, leading to an inability of wound macrophages to polarize to an M1 phenotype effectively, which in turn

关键词： Biological sciences   Components of the immune system   Immunology   Specialized functions of cells  

摘要： Chimeric antigen receptors – natural killer (CAR-NK) cells are a promising new cancer treatment approach. They possess distinct benefits over CAR-T cells, including an intrinsic ability to differentiate between malignant and non-malignant cells, and a lower risk of graft-versus-host disease. Here, we evaluated two CAR-NK-92 cell lines, targeting either CD276 or HER2, and their potential on-target/off-tumor effects in vitro. CD276-directed CAR-NK-92 cells showed little dependence on target antigen density, while HER2-directed CAR-NK-92 displayed a pronounced dependence on target antigen density, mostly sparing target cells with low amounts of HER2. The activity of both cell lines was modulated by the expression of HLA-I on target cells, ultimately reducing their activity against non-malignant cells. Lower modulation of activity of HER2-directed CAR-NK-92 can be explained by the lower surface expression of inhibitory NK receptors, such as NKG2A and ILT-2. These results underscore the importance of thoroughly testing new cell products to fine-tune anti-cancer activity, while limiting potential on-target/off-tumor toxicity. © 2025 The Authors

关键词： Components of the immune system   Immunology   Transcriptomics  

摘要： Janus kinases (JAK) mediate signaling pathways of multiple cytokines, including interferon-gamma (IFN-gamma), which plays a pivotal role in rheumatoid arthritis (RA) pathogenesis. Although JAK inhibitors (JAKi) have demonstrated efficacy for RA, their molecular effects on macrophages remain incompletely understood. We investigate the impact of JAKi on IFN-gamma-induced gene expression in human macrophages, uncovering that JAKi selectively modulates only a subset of IFN-gamma-induced genes. Integrated transcriptomic and epigenomic analyses demonstrate that JAKi effectively inhibits IFN-gamma signature genes associated with IRF1-STAT1-depen-dent accessible chromatin regions. However, genes regulated by AP-1 and C/EBP remain insensitive to JAKi and overlap significantly with TNF-induced genes. Single-cell analysis of RA patient samples identifies macrophage subpopulations with variable JAKi sensitivity. Certain JAKi-insensitive genes in IFN-gamma-primed macrophages are suppressed by JNK inhibitors. Our findings elucidate JAKi responsiveness mechanisms through IFN-gamma-induced epigenomic remodeling, providing insights into inflammatory regulation in RA and suggesting strategies to overcome JAKi resistance.

关键词： immunotherapy   T cell immunity   pMHC-I   gene level regulation   epigenetic level regulation   protein level regulation  

摘要： T cell immune responses are triggered by antigenic peptides presented through major histocompatibility complex class Is (pMHC-Is), which play an important role in the genesis, development, and therapy of tumors. The capacity of a specific pMHC-I to elicit T cell responses is deeply influenced by its expression level (quantity) and its immunogenicity (quality). Tumor cells can evade T cell immunity by down-regulating the quantity of pMHC-Is or selectively eliminating highly immunogenic antigenic peptides. Augmenting the quantity or quality of pMHC-Is is essential for tumor immunotherapy. However, the complexity of pMHC-I regulation and tumor heterogeneity pose challenges to clinical strategies. Consequently, developing approaches grounded in comprehensive analyses of pMHC-I regulatory mechanisms remains a focal point in the research of T cell immunity. In this review, we discuss how tumors modulate their surface pMHC-Is through genetic, epigenetic, and proteomic mechanisms and summarize potential therapeutic strategies targeting these mechanisms, which may provide a valuable reference for the development of novel tumor immunotherapies based on pMHC-I *** cells can achieve immune escape by interfering with the quantity and quality of pMHC-Is, and corresponding immunotherapy can also be achieved by the regulation of pMHC-Is.

关键词： Evolutionary biology   Genomics   Ornithology  

摘要： The major histocompatibility complex (MHC) genes are vital for the adaptive immune response in vertebrates and are widely used in conservation genetics to represent adaptive variation. Accurate genotyping of MHC alleles is essential for effective conservation, particularly for endangered species like the yellow cardinal (Gubernatrix cristata). However, the absence of locus-specific primers and the highly repetitive nature of these genes present a technical limitation when using short-read sequencing technologies. We produced the first high-quality long-read reference genome for the yellow cardinal. This genome reveals sustained high genome-wide heterozygosity despite inbreeding, with homozygosity patterns and effective population size estimates indicating a long-term decline. We identified seven genomic MHC-I loci, while amplicon sequencing with non-locus specific primers had not confirmed more than two MHC-I loci. Our study also revealed mismatches in primer binding sites across multiple loci, emphasizing the need for high-quality, long-read genomic data to understand the genomic architecture of MCH and to accurately assess locus specific MHC variation.

关键词： Certolizumab pegol   Rheumatoid arthritis   Rheumatoid factor   Tumor necrosis factor inhibitor  

摘要： IntroductionAlthough the efficacy of tumor necrosis factor inhibitors (TNFi) is reduced in patients with rheumatoid factor (RF)-high rheumatoid arthritis (RA), certolizumab pegol (CZP), lacking the Fc portion, may not be affected. This study aimed to compare CZP with Fc-containing TNFi and investigate whether RF levels affect the efficacy of CZP in patients with *** multicenter retrospective study involved patients with RA (n = 1010) who received TNFi with concomitant methotrexate (MTX). Patients were categorized by baseline RF quartiles. The primary endpoint was the Simplified Disease Activity Index (SDAI) remission rates at 26 weeks for patients treated with CZP and those receiving Fc-containing TNFi. The secondary endpoint compared the efficacy of CZP and adalimumab (ADA) in each RF quartile using propensity score-based inverse probability of treatment weighting (PS-IPTW).ResultsIn the overall cohort, the SDAI remission rate was the lowest in Q4 (RF >= 136.45 IU/mL). In Q4, multivariable logistic regression analysis showed that only the introduction of CZP was significantly associated with remission at 26 weeks. The Fc-containing TNFi group had significantly lower SDAI remission rates in Q4 compared with Q1-Q3. Conversely, the SDAI remission rates were similar between the two groups treated with CZP. After PS-IPTW adjustment in Q4, CZP-treated patients showed a significantly lower SDAI and higher remission rate (36.6%) compared with the ADA-treated patients (24.5%) (p = 0.0172). No significant differences in SDAI remission rates were observed between the two groups in *** may be more effective than Fc-containing TNFi in patients with RA and high RF levels.