FCGR1A(CD64) expression on monocyte subsets and FIL1Z(IL-37) serum level as biomarkers of rheumatoid arthritis activity: A case controlled study and in silico analysisMokhtar, Abd El-Fattah, Hussein
et alPathol Res Pract (2025) 269, 155910
Abstract: Rheumatoid arthritis (RA) is one of the most common chronic autoimmune diseases. Chronic joint inflammation and bone destruction were shown to be caused by expanded monocytes in RA affected individuals. Interleukin-37 which known as FIL1Z(IL-37) is a well-known anti-inflammatory cytokine that plays a negative regulatory role of inflammation in RA. A total of 48 RA patients were divided equally into active RA group and stable RA group using the Disease Activity score (DAS)-28 score. Twenty-four age-and sex-matched healthy subjects were enrolled as controls. The expression level of Fc gamma receptor IA (FCGR1A(CD64)) on monocytes and their subsets in peripheral blood were assessed by flow cytometry (FC) and serum levels of FIL1Z(IL-37) were measured by ELISA. The mean fluorescence intensity (MFI) of FCGR1A(CD64) expressing classical and intermediate monocyte subsets and serum levels of FIL1Z(IL-37) were significantly elevated in RA patients compared to the control and positively correlated with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and DAS-28 scores. The MFI of FCGR1A(CD64) expressing classical monocyte and serum levels of FIL1Z(IL-37) were significantly elevated in the active RA group compared to the stable RA group. The serum concentration of FIL1Z(IL-37) revealed very high specificity but limited sensitivity in discriminating between active and stable RA patients. Our results demonstrate a strong correlation between serum levels of FIL1Z(IL-37) and FCGR1A(CD64) expression on activated monocytes and their subsets in peripheral blood of RA patients. The results also depict that activated monocytes and their subsets may contribute to the elevated levels of FIL1Z(IL-37) during an active disease status to counter-act the inflammatory process.Copyright © 2025 Elsevier GmbH. All rights reserved.
The significant role of IL-15, IL-22, IL-37, and caspase 9 in polycystic ovary syndrome: A case-control study in a sample of Iraqi womenMohammed, Sulaiman, Alabassi
et alJ Genet Eng Biotechnol (2025) 23 (1), 100462
Abstract: The study aims to evaluate the significant role of interleukin 15 (IL-15), IL-22, IL-37, and Caspase 9 gene expression in polycystic ovary syndrome (PCOS), focusing on the underlying mechanisms and potential diagnostic or therapeutic implications. Peripheral blood has been collected, and serum was separated for the evaluation of the serum IL-15, IL-22, and IL-37. The ELISA technique has been carried out to determine the serum levels of understudied factors mentioned above in Iraqi women patients diagnosed with PCOS (No. = 90) via a specialized gynecologist and healthy fertile women (No. = 48) as a control group. In addition, a genetic study on the expression of the caspase 9 gene in these patients had been performed. The data reveals statistically significant differences in interleukin levels in PCOS patients versus the control group. Specifically, the PCOS group exhibits significantly higher levels of IL-15 and IL-22 as compared to the control group. Conversely, the PCOS group shows significantly lower levels of IL-37 compared to the control group. The results showed no statistically significant difference in the mean expression of the Caspase 9 gene when comparing these fold graduations. However, it's worth noting that a higher fold frequency was observed in both the PCOS and control groups, with 57.1 % and 60 %, respectively, having folds less than 1. The distribution of folds varied across other categories was also addressed. Additionally, there was a notable difference in the frequency of 11.4 % in the PCOS group compared to 2 % in the control group for folds greater than 9. The findings suggest that interleukins, particularly IL-22 and IL-37, hold promise as diagnostic markers for distinguishing PCOS from healthy conditions. However, the potential diagnostic utility of the Caspase 9 gene expression was not confirmed in this study.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
AAV9-delivery of interleukin-37b gene prevents recurrent herpetic stromal keratitis via the SIGIRR pathway in miceWu, Liu, Wang
et alJ Control Release (2025) 381, 113600
Abstract: Ocular herpes simplex virus type I (HSV-1) infection can lead to herpes stromal keratitis (HSK), a condition that may recur throughout a person's life and often results in progressive corneal scarring, which ultimately causes visual impairment. Since existing antiviral agents are ineffective against recurrent HSK, we aimed to explore a strategy to prevent or control recurrent HSK. Adeno-associated virus (AAV) delivery system can transduce target genes into corneal epithelial cells and establish long-term stable gene expression, and providing a promising approach for the prevention and management of recurrent HSK. In this study, interleukin-37 (IL-37), an anti-inflammatory factor, is identified as a therapeutic agent for recurrent HSK via the SIGIRR pathway. AAV9-IL-37bΔ1-45 gene therapy prevents recurrent HSK in HSV-1 latently infected mice and alleviates corneal injury in mice with HSK. In conclusion, our present study establishes a strong foundation for the prevention of recurrent HSK through AAV9-IL-37bΔ1-45 gene therapy.Copyright © 2024. Published by Elsevier B.V.
Fluoride-Mediated Immune Damage Through Cytokine Network Regulation of TregsLiu, Zhu, Zhang
et alToxics (2025) 13 (2)
Abstract: Long-term fluoride exposure can induce inflammatory responses in various tissues of the body, thereby affecting the inflammatory microenvironment. To explore how fluoride induces changes in immune function within this microenvironment, this study collected baseline information and biological samples from participants in areas with the drinking water type of fluorosis, and simultaneously established Wistar rat models with a 12-week and 24-week fluoride exposure, as well as a 12-week fluoride exposure followed by 12-week pure water feeding regimen. Luminex multiplex assays and enzyme-linked immunosorbent assays (ELISAs) were used to measure cytokine expression levels. Subsequently, correlation analysis, multiple linear regression, and mediation analysis were employed to explore the long-term effects induced by the complex cytokine network during fluoride exposure. The population survey results indicated that fluoride suppressed the expression of pro-inflammatory factors such as Interleukin-2 (IL-2), Interleukin-12 (IL-12), Interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and anti-inflammatory factors such as Interleukin-4 (IL-4), Interleukin-13 (IL-13), and Interleukin-37 (IL-37), while promoting an increase in the proportion of regulatory T cells (Tregs) in peripheral blood. Among these, IL-2 and IFN-γ mediated the fluoride-induced peripheral Tregs expansion. Animal experiments indicate that the proportion of Tregs in peripheral blood and immune organs increases in a time-dependent manner with fluoride exposure. After reducing the fluoride concentration in the drinking water of rats, the number of Tregs remained significantly elevated. The changes in Treg numbers in the 12-week fluoride feeding group, 24-week fluoride feeding group, and 12-week fluoride feeding followed by 12-week water improvement group were related to the cytokine levels. Therefore, the impact of fluoride on the immune homeostasis has cumulative and long-term effects, and may be related to the accumulation and migration of Tregs induced by fluoride in an inflammatory environment, mediated by cytokines.
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