Browsing by Author "Erdem, Serife"

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Alantolactone Ameliorates Graft Versus Host Disease in Mice
(Elsevier, 2024) Odabas, Gul Pelin; Aslan, Kubra; Suna, Pinar Alisan; Kendirli, Perihan Kader; Erdem, Serife; Cakir, Mustafa; Unal, Ekrem
The anti-inflammatory and immunosuppressive drugs which are used in the treatment of Graft-versus-Host Disease (GVHD) have limited effects in controlling the severity of the disease. In this study, we aimed to investigate the prophylactic effect of Alantolactone (ALT) in a murine model of experimental GVHD. The study included 4 BALB/c groups as hosts: Naive (n = 7), Control GVHD (n = 16), ALT-GVHD (n = 16), and Syngeneic transplantation (n = 10). Busulfan (20 mg/kg/day) for 4 days followed by cyclophosphamide (100 mg/kg/day) were administered for conditioning. Allogeneic transplantation was performed with cells collected from mismatched female C57BL/6, and GVHD development was monitored by histological and flow cytometric assays. Additionally, liver biopsies were taken from GVHD patient volunteers between ages 2-18 (n = 4) and non-GVHD patients between ages 2-50 (n = 5) and cultured ex vivo with ALT, and the supernatants were used for ELISA. ALT significantly ameliorated histopathological scores of the GVHD and improved GVHD clinical scores. CD8+ T cells were shown to be reduced after ALT treatment. More importantly, ALT treatment skewed T cells to a more naive phenotype (CD62L+ CD44-). ALT did not alter Treg cell number or frequency. ALT treatment appears to suppress myeloid cell lineage (CD11c+). Consistent with reduced myeloid lineage, liver and small intestine levels of GM-CSF were reduced in ALT-treated mice. IL-6 gene expression was significantly reduced in the intestinal tissue. Ex vivo ALT-treated liver biopsy samples from GVHD patients showed a trend of decrease in proinflammatory cytokines but there was no statistical significance. Collectively, the data indicated that ALT may have immunomodulatory actions in a preclinical murine GVHD model.
Schisandrin B Treatment After Disease Induction Slightly Improved Experimental Autoimmune Encephalomyelitis
(Sage Publications Ltd, 2023) Yetkin, Mehmet Fatih; Erdem, Serife; Azizoglu, Zehra Busra; Demir, Busra Seniz; Acikgoz, Eda; Cakir, Mustafa; Eken, Ahmet
Temporal Overexpression of Il-22 and Reg3γ Differentially Impacts the Severity of Experimental Autoimmune Encephalomyelitis
(Wiley, 2021) Eken, Ahmet; Erdem, Serife; Haliloglu, Yesim; Zehra Okus, Fatma; Cakir, Mustafa; Fatih Yetkin, Mehmet; Canatan, Halit
IL-22 is an alpha-helical cytokine which belongs to the IL-10 family of cytokines. IL-22 is produced by ROR gamma t+ innate and adaptive lymphocytes, including ILC3, gamma delta T, iNKT, Th17 and Th22 cells and some granulocytes. IL-22 receptor is expressed primarily by non-haematopoietic cells. IL-22 is critical for barrier immunity at the mucosal surfaces in the steady state and during infection. Although IL-22 knockout mice were previously shown to develop experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), how temporal IL-22 manipulation in adult mice would affect EAE course has not been studied previously. In this study, we overexpressed IL-22 via hydrodynamic gene delivery or blocked it via neutralizing antibodies in C57BL/6 mice to explore the therapeutic impact of IL-22 modulation on the EAE course. IL-22 overexpression significantly decreased EAE scores and demyelination, and reduced infiltration of IFN-gamma+IL-17A+Th17 cells into the central nervous system (CNS). The neutralization of IL-22 did not alter the EAE pathology significantly. We show that IL-22-mediated protection is independent of Reg3 gamma, an epithelial cell-derived antimicrobial peptide induced by IL-22. Thus, overexpression of Reg3 gamma significantly exacerbated EAE scores, demyelination and infiltration of IFN-gamma+IL-17A+ and IL-17A+GM-CSF+Th17 cells to CNS. We also show that Reg3 gamma may inhibit IL-2-mediated STAT5 signalling and impair expansion of Treg cells in vivo and in vitro. Finally, Reg3 gamma overexpression dramatically impacted intestinal microbiota during EAE. Our results provide novel insight into the role of IL-22 and IL-22-induced antimicrobial peptide Reg3 gamma in the pathogenesis of CNS inflammation in a murine model of MS.