Polymorphisms in IL-10- and IL-22-Binding Protein Genes as Genetic Predictors of the Direct-Acting Antivirals Treatment Response in Patients with Chronic Hepatitis C VirusSaleem, Akbar, Jilkova
et alJ Interferon Cytokine Res (2025)
Abstract: Cytokines are crucial in controlling inflammation during viral infection, particularly infection with the hepatitis C virus (HCV). Cytokine genetic polymorphisms can change how the immune system responds to this infection. We investigated how the HCV infection treatment was affected by single nucleotide polymorphisms in these genes. The goal of this study was to examine any connections between the cytokine gene polymorphisms for interleukins (IL)-22-binding protein rs6570136, as well as IL-10 rs1800872 and rs1878672 in the Pakistani population and responsiveness to direct-acting antivirals (DAAs) treatment. This study evaluated 155 participants, which included 55 patients who achieved sustained virologic response (SVR), 40 relapse patients, and 60 healthy controls, to assess and compare the clinical parameters. The SVR and relapse groups were compared for their allelic and genotypic frequencies. We discovered that the SVR and the relapse groups had significantly different genotype frequencies for IL-10 rs1800872 and IL-22BP rs6570136 in the Pakistani population. The G/G genotype in rs6570136 and A/A genotype in rs1800872 were significantly associated with relapse following DAA therapy, with P values 0.002 and 0.0004, respectively. In contrast, rs1878672 showed no significant correlation with HCV relapse, P = 0.63.
Brusatol ameliorates intestinal mucosal injury in ulcerative colitis via activating IL-22/STAT3 pathwayXu, Chen, Hu
et alInt Immunopharmacol (2025) 153, 114482
Abstract: Brusatol (BR) is an active compounds isolated from Brucea javanica, a Chinese herbal medicine that is famous for its anti-diarrheal effect. We have previously reported that BR mitigated inflammation in murine ulcerative colitis (UC) models. However, BR's role in intestinal mucosal healing, which is recently established as central strategy for the prevention and treatment of UC, remains unknown. In this study, the ameliorative effect of BR on intestinal mucosal damage was investigated in DSS-induced UC mice. BR significantly alleviated colitis symptoms, improved intestinal barrier function by preventing loss of goblet cells and downregulation of mucins and tight junction proteins, as well as maintained proliferative and apoptotic homeostasis in the colonic epithelium of UC mice. Mechanistically, BR enhanced the level and secretion of IL-22, but inhibited IL-22BP, an inhibitory protein of IL-22, in the blood serum and intestinal tissues of UC mice, as well as in MNK3 cells which is an effective cell model for studying ILC3s. Additionally, BR elevated the expressions of receptors for IL-22 (IL-10R2 and IL-22R1), and activated its downstream STAT3 signaling pathway. Furthermore, the involvement of IL-22 was further investigated by using recombinant IL-22 (rIL-22) and IL-22 antibody (anti-IL-22). BR demonstrated comparable effects with rIL-22 on alleviating intestinal inflammation and repairing intestinal mucosal injury. Treatment with anti-IL-22 abrogated the mucosal protective effects of BR. The present findings shed novel insights into the role of BR in intestinal mucosal healing via activating IL-22/STAT3 signaling pathway in UC.Copyright © 2025 Elsevier B.V. All rights reserved.
Th22 cells promote the transition from homeostatic to reactive microglia in diabetic encephalopathyYu, Yu, Wang
et alActa Diabetol (2024)
Abstract: Diabetic encephalopathy (DE) is one of the most serious complications of diabetes mellitus (DM), and its pathogenesis has not yet been clarified. Th22 cells are a newly discovered class of CD4+ T cells that play important roles in inflammatory, autoimmune and infectious diseases. However, it is unclear whether Th22 cells are involved in the pathogenesis of DE.We established a T2DM mouse model in vivo and cocultured Th22 cells with microglia under high glucose (HG) conditions in vitro. Cognitive dysfunction was evaluated using the Morris water maze (MWM) test; blood‒brain barrier (BBB) integrity was evaluated using the Evans blue (EB) extravasation assay; Th22 cells and IL-22 receptors were detected by immunofluorescence; and IL-1β, TNF-α, iNOS, CD86, Arg-1, and CD206 protein expression was measured by Western Blot (WB) analysis.Th22 cells passed through the BBB into the hippocampus and secreted interleukin-22 (IL-22), and the mice subsequently exhibited decreased learning and memory abilities. In the DE model, IL-22 promoted the transformation of homeostatic microglia into reactive microglia as well as the inflammatory response. Additionally, coculture of Th22 cells with BV2 microglia cultured under HG conditions increased the production of proinflammatory cytokines, and the microglia showed reactive changes. Mechanistically, IL-22Rα1 acted as a ligand, and IL-22 bound to IL-22Rα1 on microglia to drive primary microglia-induced inflammatory responses. Interestingly, interleukin-22 binding protein (IL-22BP) directly binds to IL-22Rα1 on microglia to inhibit the proinflammatory effects of IL-22.Th22 cells secrete IL-22 after passing through the BBB into the hippocampus and promote the transformation of homeostatic microglia into reactive microglia, which induces an inflammatory response, exacerbates learning and memory impairment and cognitive deficits, and contributes to and accelerates the development of DE.© 2024. The Author(s).
RelB and C/EBPα critically regulate the development of Peyer's patch mononuclear phagocytesKanaya, Jinnohara, Sakakibara
et alMucosal Immunol (2025) 18 (1), 151-161
Abstract: To establish protection against harmful foreign antigens, the small intestine harbors guardian sites called Peyer's patches (PPs). PPs take up antigens through microfold (M) cells and transfer them to the sub-epithelial dome (SED), which contains a high density of mononuclear phagocytes (MPs), for T cell-priming. Accumulating evidence indicates that SED-MPs have unique functions other than T cell-priming to facilitate mucosal immune responses; however, the crucial factors regulating the functions of SED-MPs have not been determined. Here we performed transcriptome analysis, and identified the gene signatures of SED-MPs. Further data interpretation with transcription factor (TF) enrichment analysis estimated TFs responsible for the functions of SED-MPs. Among them, we found that RelB and C/EBPα were preferentially activated in SED-MPs. RelB-deficiency silenced the expression of IL-22BP and S100A4 by SED-MPs. On the other hand, C/EBPα-deficiency decreased the expression of lysozyme by SED-MPs, resulting the increased invasion of orally administered pathogenic bacteria into PPs and mesenteric lymph nodes. Our findings thus demonstrate that RelB and C/EBPα are essential to regulate the functions of SED-MPs.Copyright © 2024. Published by Elsevier Inc.
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