Mesenchymal Stem Cells Upregulate the Expression of PD-L1 But Not VDR in Dendritic Cells
| Autor: | Ali Moravej, Maryam Khosravi, Behrouz Gharesi-Fard, Ramin Yaghobi, Mehdi Kalani, Negar Azarpira, Amir-Hasan Zarnani, Bita Geramizadeh, Mohammad Hossein Karimi |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Interleukin 2 Isoantigens T-Lymphocytes medicine.medical_treatment Immunology Lymphocyte Activation Calcitriol receptor B7-H1 Antigen Immune tolerance Immunomodulation Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation PD-L1 Immune Tolerance medicine Animals Cells Cultured Cell Proliferation Mice Inbred BALB C biology Mesenchymal stem cell Mesenchymal Stem Cells Dendritic Cells General Medicine Coculture Techniques Interleukin-10 Up-Regulation Interleukin 10 030104 developmental biology Cytokine biology.protein Cancer research Interleukin-2 Receptors Calcitriol 030215 immunology medicine.drug |
| Zdroj: | Immunological Investigations. 46:80-96 |
| ISSN: | 1532-4311 0882-0139 |
| DOI: | 10.1080/08820139.2016.1225757 |
| Popis: | Mesenchymal stem cells (MSCs) show immunomodulatory functions. But the exact mechanism underlying these activities of MSCs is still not completely understood. There have been a few studies which have assessed the effects of these cells on dendritic cells (DCs) function. Given the importance of programmed cell death receptor-1 (PD-L1) and vitamin D receptor (VDR) expression in induction of tolerance in DCs, we were encouraged to investigate if one of the immunomodulatory functions of MSCs could be inducing upregulation of PD-L1 and VDR on DCs or not.DCs were co-cultured with MSCs or treated with them in transwell plates in the presence or absence of Lipopolysaccharide (LPS). Expression of PD-L1 and VDR mRNA and proteins in treated DCs were assessed by Real-time PCR and Western blot techniques. Furthermore, treated DCs were co-cultured with allogeneic T-cells, and T-cell proliferation and cytokine secretions in co-culture supernatants were assessed.The results showed that PD-L1 but not VDR expression is significantly upregulated in the DCs co-cultured with MSCs. Furthermore, cell-to-cell contact and also presence of maturation inducers like LPS is necessary for this function. Moreover, our results indicated that MSCs could induce tolerogenic DCs (TolDCs) which could decrease the secretion of IL-2 by T-cells and inhibit T-cell proliferation as well as increase secretion of IL-10.Overall, our results show that MSCs may have several suppressive effects on immune responses by induction of TolDCs expressing more PD-L1 immunomodulatory molecule and change the cytokines profile of DCs and T-cells. |
| Databáze: | OpenAIRE |
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