Browsing by Author "Eken, Ahmet"

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The Number and Activity of Cd3+tcr Vα7.2+cd161+< Cells Are Increased in Children With Acute Rheumatic Fever
(Elsevier Ireland Ltd, 2021) Ozkaya, Mehmet; Baykan, Ali; Cakir, Mustafa; Vural, Cagdas; Sunkak, Suleyman; Unal, Ekrem; Eken, Ahmet
Background: Acute rheumatic fever (ARF) is an autoimmune disease caused by group A beta-hemolytic streptococci (GAS) and may develop into rheumatic heart disease (RHD). The pathogenesis of ARF and RHD involves molecular mimicry and antibody-mediated mechanisms. T cell involvement is described in various stages of the disease. Mucosal associated invariant T (MATT) cells are enriched at the mucosa and are present in the blood and may be activated by GAS. Methods: In this study, we investigated the quantity and activity of CD3(+) TCRV alpha 7.2(+) CD161(+) cells in the active and recovered ARF patients and healthy controls. Twenty newly diagnosed, 20 recovered-ARF children, and 20 healthy controls were enrolled in the study. Peripheral blood (PB) mononuclear cells were isolated by Ficoll-Paque density gradient. CD4(+) CD4(-) subsets of CD3(+) TCRV alpha 7.2(+) CD161(+) cells and IFN-gamma and TNF-alpha production were quantified by Flow cytometry. Results: Acute and recovered ARF patients had significantly elevated the number of CD3(+) TCRV alpha 7.2(+) CD161(+) cells in their PB. Both CD4(+) and CD4(-) subsets were increased. Moreover, total cell numbers were significantly higher in the recovered patients PB compared with active ARE patients. In addition, CD3(+) TCRV alpha 7.2(+) CD161(+) cells in both acute and recovered patients produced significantly more IFN-gamma and TNF-alpha. Non-MALT total CD3(+) T cell, CD4(+) and CD4(-) T cell subsets were also increased in active and recovered ARF patients and they also produced more IFN-gamma and TNF-alpha. Conclusion: Our data reveal that CD3(+) TCRV alpha 7.2(+) CD161(+) cells are elevated and actively producing IFN-gamma and TNF-alpha in acute and recovered ARF patients and may contribute to ARF pathology. (C) 2021 Elsevier B.V. All rights reserved.
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.