Cyclosporine A, in Contrast to Rapamycin, Affects the Ability of Dendritic Cells to Induce Immune Tolerance Mechanisms.
Maja MachcińskaMonika KoturAleksandra JankowskaMarta Maruszewska-CheruiyotArtur ŁaskiZuzanna KotkowskaKatarzyna BocianGrażyna Korczak-KowalskaPublished in: Archivum immunologiae et therapiae experimentalis (2021)
Following organ transplantation, it is essential that immune tolerance is induced in the graft recipient to reduce the risk of rejection and avoid complications associated with the long-term use of immunosuppressive drugs. Immature dendritic cells (DCs) are considered to promote transplant tolerance and may minimize the risk of graft rejection. The aim of the study was to evaluate the effects of immunosuppressive agents: rapamycin (Rapa) and cyclosporine A (CsA) on generation of human tolerogenic DCs (tolDCs) and also to evaluate the ability of these cells to induce mechanisms of immune tolerance. tolDCs were generated in the environment of Rapa or CsA. Next, we evaluated the effects of these agents on surface phenotypes (CD11c, MHC II, CD40, CD80, CD83, CD86, CCR7, TLR2, TLR4), cytokine production (IL-4, IL-6, IL-10, IL-12p70, TGF-β), phagocytic capacity and resistant to lipopolysaccharide activation of these DCs. Moreover, we assessed ability of such tolDCs to induce T cell activation and apoptosis, Treg differentiation and production of Th1- and Th2-characteristic cytokine profile. Data obtained in this study demonstrate that rapamycin is effective at generating maturation-resistant tolDCs, however, does not change the ability of these cells to induce mechanisms of immune tolerance. In contrast, CsA affects the ability of these cells to induce mechanisms of immune tolerance, but is not efficient at generating maturation-resistant tolDCs.
Keyphrases
- dendritic cells
- cell cycle arrest
- induced apoptosis
- immune response
- toll like receptor
- endoplasmic reticulum stress
- regulatory t cells
- inflammatory response
- magnetic resonance
- cell death
- oxidative stress
- endothelial cells
- signaling pathway
- pi k akt
- stem cells
- electronic health record
- epithelial mesenchymal transition
- contrast enhanced
- cell proliferation
- artificial intelligence
- cell therapy