Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro
<em><strong>Objective(s):</strong></em> 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-deriv...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2020-03-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | http://ijbms.mums.ac.ir/article_14559_91ff436ba6d68a96dfd5d7d07e867b4f.pdf |
| _version_ | 1818385283894214656 |
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| author | Tahereh kalantari Bogoljub Ciric Eskandar Kamali-Sarvestani Abdolmohamad Rostami |
| author_facet | Tahereh kalantari Bogoljub Ciric Eskandar Kamali-Sarvestani Abdolmohamad Rostami |
| author_sort | Tahereh kalantari |
| collection | DOAJ |
| description | <em><strong>Objective(s):</strong></em> 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. <br /><em><strong>Materials and Methods:</strong></em> 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. <br /><em><strong>Results:</strong></em> 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. <br /><em><strong>Conclusion:</strong></em> 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. |
| first_indexed | 2024-12-14T03:35:42Z |
| format | Article |
| id | doaj.art-04c78ba2810448878768b5ba83e75221 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-12-14T03:35:42Z |
| publishDate | 2020-03-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-04c78ba2810448878768b5ba83e752212022-12-21T23:18:37ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742020-03-0123328729210.22038/ijbms.2020.36160.861514559Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitroTahereh kalantari0Bogoljub Ciric1Eskandar Kamali-Sarvestani2Abdolmohamad Rostami3Diagnostic 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 Sciences, Shiraz, Iran|Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USADepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USAImmunology Department, Shiraz University of Medical Sciences, Shiraz, IranDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA 19107, USA<em><strong>Objective(s):</strong></em> 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. <br /><em><strong>Materials and Methods:</strong></em> 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. <br /><em><strong>Results:</strong></em> 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. <br /><em><strong>Conclusion:</strong></em> 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.http://ijbms.mums.ac.ir/article_14559_91ff436ba6d68a96dfd5d7d07e867b4f.pdfcd40cd40koil-23il-23p19kotolerogenic dc |
| spellingShingle | Tahereh kalantari Bogoljub Ciric Eskandar Kamali-Sarvestani Abdolmohamad Rostami Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro Iranian Journal of Basic Medical Sciences cd40 cd40ko il-23 il-23p19ko tolerogenic dc |
| title | Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro |
| title_full | Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro |
| title_fullStr | Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro |
| title_full_unstemmed | Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro |
| title_short | Bone marrow dendritic cells deficient for CD40 and IL-23p19 are tolerogenic in vitro |
| title_sort | bone marrow dendritic cells deficient for cd40 and il 23p19 are tolerogenic in vitro |
| topic | cd40 cd40ko il-23 il-23p19ko tolerogenic dc |
| url | http://ijbms.mums.ac.ir/article_14559_91ff436ba6d68a96dfd5d7d07e867b4f.pdf |
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