TY - JOUR ID - 14559 TI - Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - kalantari, Tahereh AU - Ciric, Bogoljub AU - Kamali-Sarvestani, Eskandar AU - Rostami, Abdolmohamad AD - Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran AD - Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA AD - Immunology Department, Shiraz University of Medical Sciences, Shiraz, Iran Y1 - 2020 PY - 2020 VL - 23 IS - 3 SP - 287 EP - 292 KW - CD40 KW - CD40KO KW - IL-23 KW - IL-23p19KO KW - Tolerogenic DC DO - 10.22038/ijbms.2020.36160.8615 N2 - 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. UR - https://ijbms.mums.ac.ir/article_14559.html L1 - https://ijbms.mums.ac.ir/article_14559_91ff436ba6d68a96dfd5d7d07e867b4f.pdf ER -