Title of article :
Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro
Author/Authors :
Kalantari, Tahereh Diagnostic Laboratory Sciences and Technology Research Center - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz - Department of Laboratory Sciences - School of Paramedical Sciences - Shiraz University of Medical Sciences, Shiraz - Department of Neurology - Thomas Jefferson University - Philadelphia - PA 19107, USA , Ciric, Bogoljub Department of Neurology - Thomas Jefferson University - Philadelphia - PA 19107, USA , Kamali-Sarvestani, Eskandar Immunology Department - Shiraz University of Medical Sciences, Shiraz , Rostami, Abdolmohamad Department of Neurology - Thomas Jefferson University - Philadelphia - PA 19107, USA
Abstract :
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.
Keywords :
CD40 , CD40KO , IL-23 , IL-23p19KO , Tolerogenic DC
Journal title :
Astroparticle Physics