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关键词： B cell   differentiation   exosomes   IL-10   mesenchymal stem cells  

摘要： The role of IL-10-producing regulatory B cells in inflammatory diseases has recently gained substantial attention. Here, we evaluated the function of mouse bone marrow mesenchymal stem cell-derived exosomes (BMMSC-Exos) and their effect on B-cell differentiation. This study aimed to establish an association between BMMSC-Exos and purified B cells and further explored the anti-inflammatory effect of B10 cells. The expression of inflammatory factors, such as IL-1 beta, TNF-alpha, and bone metabolism-related factors, including RANKL, OPG, and secreted IL-10, was investigated by RT-qPCR and ELISA. Populations of CD1dhighCD5+ B cells were analyzed by flow cytometry and immunofluorescence. Cell viability was assessed by CCK8 assay. The results showed that when B cells were separated from BMMSCs by Transwell, IL-1 beta, TNF-alpha, and RANKL were downregulated, whereas IL-10, OPG/RANKL, and CD1dhighCD5+ Breg proportion were upregulated in the cocultured groups. Conversely, when B cells were cultured with BMMSC-Exos, increasing concentrations of exosomes increased the proportion of CD1dhighCD5+ and IL-10+CD45+ Bregs;however, the secretion of both pro-inflammatory cytokines and IL-10 were decreased. We found that BMMSC-Exos induce the differentiation of B cells toward the CD1dhighCD5+ and IL-10+CD45+ Breg phenotype but cannot increase the secretion of IL-10 in vitro.

关键词： Asthma   IL-36   type 2   non-type 2   IL-6   pulmonary function   acute exacerbation  

摘要： Background: The IL-36 subfamily, a member of the IL-1 superfamily, is thought to promote type 2 (T2) and non-T2 inflammation and involved in autoimmune and airway disease progression. However, its role in asthma remains unclear. Objective: We sought to determine the contribution of the IL-36 subfamily to the clinical manifestation of asthma. Methods: The levels of serum IL-36a, IL-36b, and IL-36y, recognized as IL-36 subfamily agonists, and IL-36 receptor antagonist (IL-36Ra) and IL-38, recognized as IL-36 subfamily antagonists, were measured by ELISA in 110 asthma patients (55 with nonsevere and 55 with severe asthma) aged >_20 years and 31 healthy individuals. The association of IL-36 with clinical indices and inflammatory mediators was examined. The characteristics of high and low IL-36 subgroups were explored. Results: IL-36a, IL-36y, and IL-36Ra levels were significantly higher in asthma patients, especially patients with severe asthma, than in healthy controls. The high IL-36y group exhibited lower Asthma Control Test scores (P 5 .01), more frequent asthma exacerbations (AEs), and higher hazard ratio for AEs. The high IL-36Ra group exhibited higher values of forced expiratory volume in 1 second, more frequent severe AEs, and higher hazard ratio for severe exacerbations. The IL36 cytokine levels, except for IL 36a, were positively correlated with IL-6, IL-13, IL-17, and/or IFN-y levels. IL-36Ra was positively correlated with age-adjusted forced expiratory volume and forced vital capacity. Conclusion: A systemically high IL-36 level is associated with asthma severity and with both T2 and non-T2 cytokines, and it implies poor condition and enhancement of risk of AEs in asthma patients. (J Allergy Clin Immunol Global 2025;4:100419.)

关键词： Interleukin-18   systemic lupus erythematosus   genetic susceptibility   clinical manifestation  

摘要： Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex etiology. Interleukin-18 (IL-18) possesses pro-inflammatory properties and plays a central role in the development of SLE. In this study, we assessed the association between two functional variants that affect the expression of IL-18, namely -607C > A (rs1946518) and -137G > C (rs187238), and the risk of SLE development. Methods: As a case-control study, 251 peripheral blood samples were collected from 121 SLE patients and 130 healthy participants. Genotyping of these polymorphisms was performed using the high-resolution melting (HRM) method, which employs real-time polymerase chain reaction. Results: Our findings revealed a significant association between the AA genotype and A allele in rs1946518, showing a decreased risk of SLE (AA vs CC;OR: 0.386;95% CI [0.174-0.828], A vs C;OR: 0.548;95% CI [0.369-0.809]). Analogously, the CC genotype and C allele in rs187238 exhibited a similar trend (CC vs GG;OR: 0.240;95% CI [0.055-0.803], C vs G;OR: 0.604;95% CI [0.390-0.928]), indicating a reduced risk of SLE Moreover, SLE subjects with the protective allele in rs1946518 (AA + AC) demonstrated significantly lower levels of CRP, and Anti-dsDNA, suggesting lower disease activity. These patients also had a later age of onset, and a lower incidence of renal involvement and creatinine levels, indicating milder disease severity (p < .05). Conclusion: The study indicates a significant relationship between the rs1946518 and rs187238 variants in IL-18 and a reduced risk of SLE. Furthermore, rs1946518 was found to be associated with certain clinical features related to disease activity and severity.

关键词： AQP4-ab   anti-aquaporin 4 antibodies   ARD   autoimmune rheumatic disease   EBV   Epstein-Barr virus   HR   hazard ratio   IBD   inflammatory bowel disease   ICD   International Classification of Diseases   ICD-10   International Classification of Diseases, Tenth revision   IL   interleukin   KNHIS   Korean National Health Insurance Service   MS   multiple sclerosis   NMOSD   neuromyelitis optica spectrum disorder   RA   rheumatoid arthritis   RID   rare intractable disease   RR   relative risk   SLE   systemic lupus erythematosus   SS   Sjögren syndrome  

摘要： Objective: To investigate the risk of autoimmune rheumatic diseases (ARDs) in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) compared with a control population using the Korean National Health Insurance Service database. Patients and Methods: The MS/NMOSD cohorts were collected from patients registered in the Korean National Health Insurance Service database between January 1, 2010, and December 31, 2017, using the International Classification of Diseases, Tenth Revision diagnosis codes and information in the Rare Intractable Disease management program. The incidence rate and risk of ARDs that occurred after a 1year lag period was calculated and compared with that of control cohorts matched for age, sex, hypertension, diabetes mellitus, and dyslipidemia in a 1:10 ratio. Results: The incidence rates of ARDs in MS and NMOSD were 3.56 and 9.13 per 1000 person-years, respectively. The hazard ratios (HRs) of ARDs in MS and NMOSD were 5.35 (95% CI, 3.50 to 8.19) and 9.13 (95% CI, 5.83 to 14.28), respectively. The risk of Beh & ccedil;et disease (HR, 17.24;95% CI, 4.12 to 72.14), systemic lupus erythematosus (HR, 12.25;95% CI, 4.12 to 36.44), Sj & ouml;gren syndrome (HR, 6.16;95% CI, 1.80 to 21.04), and seropositive rheumatoid arthritis (HR, 3.32;95% CI, 1.78 to 6.19) was increased in MS. In NMOSD, the risk of Sj & ouml;gren syndrome (HR, 82.63;95% CI, 19.00 to 359.38), systemic lupus erythematosus (HR, 30.85;95% CI, 6.23 to 152.80), Beh & ccedil;et disease (HR, 15.36;95% CI, 2.57 to 91.93), and seropositive rheumatoid arthritis (HR, 3.86;95% CI, 1.80 to 8.31) was increased. Conclusion: The risk of ARDs was increased in MS/NMOSD, and the risk of each ARD differed between MS and NMOSD.

关键词： IL-1 beta   Sleep   Cigarette smoking   Cerebrospinal fluid   Neuroinflammation  

摘要： Objective: Inflammatory factors and cigarette smoking have been associated with sleep disorders but molecular mechanisms that regulate sleep, specifically the role of interleukin-1 beta (IL-1 beta), remain controversial. Individuals' cerebrospinal fluid (CSF) IL-1 beta, smoking behavior, and sleep data were collected to investigate how smoking may influence the relationship between CSF IL-1 beta and sleep via moderation analysis. Methods: A total of 191 Chinese male patients, including 104 non-smokers and 87 active smokers, scheduled for anterior cruciate ligament reconstructive surgery, were recruited. Pittsburgh Sleep Quality Index (PSQI) scores were collected prior to surgery, and CSF samples were obtained during preoperative lumbar puncture. Results: Active smokers compared to non-smokers exhibited higher scores across various subdimensions of PSQI, specifically poorer sleep quality, increased sleep latency, reduced sleep efficiency, and heightened sleep disturbance (all p < 0.05). Positive correlations were observed between CSF IL-1 beta levels and PSQI total scores, as well as several subdimensions of sleep (all p < 0.05) in non-smokers. In contrast, a negative correlation was observed between CSF IL-1 beta levels and sleep efficiency scores (p < 0.05) among active smokers. Moderation analysis revealed that smoking negatively moderated the relationship between CSF IL-1 beta and sleep, particularly in PSQI total scores (beta =-0.95, p < 0.001), sleep latency scores (beta =-1.05, p < 0.001), and sleep disturbance scores (beta =-0.45, p < 0.05). Conclusions: The current study found that smoking disrupts multiple subdimensions of sleep and moderates the effect of the neuroinflammatory factor CSF IL-1 beta on PSQI sleep latency and sleep disturbance scores.

摘要： Ciprofloxacin (CIP) was found to enhance pegylated G-CSF therapy (PEG, Neulasta (R))-induced survival from 30% to 85% after ionizing radiation exposure. This combined therapy significantly mitigated radiation-induced brain hemorrhage through its capability to improve platelet recovery. This study tested whether this combined treatment also mitigated gastrointestinal damage from radiation. B6D2F1 female mice were exposed to Co-60 gamma radiation. CIP was fed daily to mice for up to 14 days. PEG was injected on day 1, and then weekly up to day 14. For the early time point study, blood, femurs, spleen, and ileum were collected on days 2, 4, 9, and 15 postirradiation. Bone marrow cells were counted;spleen weights and splenocyte counts were measured;and ileum histopathology was examined and analyzed. AKT, ERK, JNK, p38, claudin 2, NF-kB, Bax, Bcl-2, and gasdermin D were measured in ileum lysates using Western blotting while miR-34a was measured by reverse transcription followed by real-time-PCR, and citrulline was measured by colorimetric assay. In serum, interleukin-18 (IL-18) was measured by Luminex assay and complement protein 3 (C3) was detected by ELISA. The bacterial DNA load in livers was measured by real-time PCR. Radiation depleted bone marrow cells in femurs beginning day 2 through day 15 postirradiation, which was mitigated by PEG or CIP1PEG on day 9 through day 15 and by CIP on day 15, respectively. Radiation exposure led to decreased spleen weight on day 2 through day 15, while PEG or CIP1PEG significantly mitigated the reduction on day 9 through day 15. Radiation exposure reduced splenocyte counts on day 2 through day 15 postirradiation, but that was mitigated by PEG or CIP1PEG on day 15. Ileum histology showed that radiation decreased villus height on day 2 through day 15;CIP mitigated the reduction on day 15, whereas PEG1CIP mitigated it on day 2 through 15. Villus widths were increased on day 2 through day 15, while PEG1CIP effectively decreased them on

关键词： Non-HLA antibody   Donor-specific antibody   Human leukocyte antigen   Liver transplantation   Rejection  

摘要： Antibodies to HLA or non-HLA antigens are associated with detrimental outcomes in organ transplants. Here, we aim to examine whether donor-specific antibodies (DSA) and non-HLA antibodies are associated with rejection in a single-center cohort of 101 pediatric liver transplant (PLTx) recipients. Rejection was found in 50/101 biopsies (49.5 %). DSA was positive in 32 paired sera and associated with rejection (HR = 2.63[1.10-6.30]). Antibodies to 3 non-HLA antigens, SNRPB (small nuclear ribonucleoprotein polypeptides B), GSTT1 (Glutathione S-transferase theta-1), and Actin were associated with rejection. Rejection was found in 22/35 cases positive for any of the three non-HLA antibodies. The presence of DSA and non-HLA antibodies was associated with an augmented risk of rejection (HR = 6.32[1.57-25.30], p < 0.01]. In conclusion, DSA or non-HLA antibodies were associated with a higher risk for rejection in PLTx recipients. When they were detected concomitantly, the risk for rejection increased significantly, indicating the synergistic effect of actions.