Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro

Authors

Tahereh Kalantari, Shiraz University of Medical Sciences, Thomas Jefferson University
Bogoljub Ciric, Thomas Jefferson UniversityFollow
Eskandar Kamali-Sarvestani, Shiraz University of Medical Sciences
Abdolmohamad Rostami, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

3-2020

Comments

This is the authors' final published version of this article, published in the Iranian Journal of Basic Medical Sciences, Volume 23, Issue 3, March 2000, pages 287-292.

The published version of this article can be accessed at https://doi.org/10.22038/IJBMS.2020.36160.8615 .

Copyright Kalantari et.al.

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.

Recommended Citation

Kalantari, Tahereh; Ciric, Bogoljub; Kamali-Sarvestani, Eskandar; and Rostami, Abdolmohamad, "Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro" (2020). Department of Neurology Faculty Papers. Paper 210.
https://jdc.jefferson.edu/neurologyfp/210

Language

English