Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro
محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 23، شماره: 3
سال انتشار: 1398
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 356
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شناسه ملی سند علمی:
JR_IJBMS-23-3_002
تاریخ نمایه سازی: 27 مرداد 1399
چکیده مقاله:
Objective(s): In addition to pro-inflammatory role, dendritic cells (DCs) can also be anti-inflammatory when they acquire tolerogenic phenotype. In this study we tested the role of CD40 and IL-23p19 in antigen presenting function of bone marrow-derived DCs (BMDCs) by comparing BMDCs derived from CD40 knockout (CD40KO-DCs) and IL-23p19 (IL-23p19KO-DCs) knockout mice with those from C57BL/6 mice (Cont-DCs). We have focused on CD40 and IL-23, as these molecules have well established pro-inflammatory roles in a number of autoimmune and inflammatory diseases. Materials and Methods: The expression of maturation markers MHC II and co-stimulatory molecules CD40, CD80, and CD86 was analyzed by flow cytometry, while the expression of CD40 and IL-23p19 was measured by RT-PCR. The capacity of BMDCs to activate CD4+ T cells was evaluated by 3H-thymidine incorporation, and the capacity of BMDCs to uptake antigen was evaluated using fluorescent OVA and flow cytometry. Results: The lack of CD40 or IL-23p19 had no effect on uptake of FITC-OVA by the DCs, confirming their immature phenotype. Moreover, CD40KO-DCs had significantly reduced capacity to stimulate proliferation of CD4+ T cells. CD4+ T cells activated by CD40KO-DCs and IL-23p19KO-DCs produced significantly less IFN-γ (P-value ≤0.05), while CD4+ T cells stimulated by IL-23p19KO-DCs produced less GM-CSF and more IL-10 than Cont-DCs. Conclusion: This study shows that CD40KO-DCs and IL-23p19KO-DCs have a marked tolerogenic potency in vitro. Future in vivo studies should determine if and to what extent DCs lacking CD40 or IL-23 have a potential to be useful in therapy of autoimmune inflammation.
کلیدواژه ها:
نویسندگان
Tahereh kalantari
Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran|Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical
Bogoljub Ciric
Department of Neurology, Thomas Jefferson University, Philadelphia, PA ۱۹۱۰۷, USA
Eskandar Kamali-Sarvestani
Immunology Department, Shiraz University of Medical Sciences, Shiraz, Iran
Abdolmohamad Rostami
Department of Neurology, Thomas Jefferson University, Philadelphia, PA ۱۹۱۰۷, USA
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