Cyclosporine A, in Contrast to Rapamycin, Affects the Ability of Dendritic Cells to Induce Immune Tolerance Mechanisms

Machcińska, Maja; Kotur, Monika; Jankowska, Aleksandra; Maruszewska-Cheruiyot, Marta; Łaski, Artur; Kotkowska, Zuzanna K.; Bocian, Katarzyna; Korczak-Kowalska, G

doi:10.1007/s00005-021-00632-7

Cited by 3 publications

(2 citation statements)

References 74 publications

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“…We have obtained similar results in our previous work concerning human monocyte-derived DCs (mo-DCs). After LPS activation, only the MFI values were significantly higher compared to immature DCs for all examined receptors: MHC II, CD40, CD80, CD83, CD86, CCR7, TLR2, TLR4 (19). With the maturation of DCs, the ability to uptake antigen decreases.…”

Section: Discussionmentioning

confidence: 91%

Heterogeneity of adherent and non‑adherent JAWS II dendritic cells

Maruszewska-Cheruiyot

Machcińska

Kierasińska

et al. 2023

Oncol Lett

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Dendritic cells (DCs) are crucial in the development of immune responses. DC JAWS II is a murine cell line frequently used in DC studies. These cells are grown in two cell fractions: Adherent and non-adherent. The present study aimed to compare these two fractions in both immature and lipopolysaccharide (LPS)-activated JAWS II cells. The present study analysed the condition, phenotype, antigen uptake capability, signalling properties and the influence on the activity of T cells using flow cytometry, mixed cell reaction and ELISA methods. Adherent immature JAWS II cells exhibited increased endocytosis and decreased activation of the Pi3K signalling pathway. After LPS activation, adherent JAWS II cells exhibited increased expression levels of CD80 and CD86 costimulatory molecules, increased endocytosis and an elevated ability to induce T cell proliferation, compared with non-adherent cells. These results demonstrated that the two fractions of JAWS II adherent and non-adherent cells exhibited different properties and this should be taken into account in the planning of research.

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Section: Discussionmentioning

confidence: 91%

Heterogeneity of adherent and non‑adherent JAWS II dendritic cells

Maruszewska-Cheruiyot

Machcińska

Kierasińska

et al. 2023

Oncol Lett

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“…To improve organ transplantation outcomes, the latest research has focused on the development of cellular therapies using Tol-DCs and immunosuppressive medications. Additionally, recent evidence has provided new perspectives on the immunopharmacology of these compounds and novel strategies for DC manipulation to promote allograft survival [98]. Polymeric nanoparticles containing ovalbumin and dexamethasone may switch DCs into Tol-DCs, inducing antigen-specific immune tolerance, as shown by Kim et al [99].…”

Section: Dendritic Cells and Transplantationmentioning

confidence: 99%

Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting

Troise,

Infante,

Mercuri

et al. 2024

Biomedicines

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Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies.

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Sinomenine promotes differentiation of induced pluripotent stem cells into immature dendritic cells with high induction of immune tolerance

Huang¹,

Jin²,

Dou³

et al. 2022

WJSC

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BACKGROUND Immature dendritic cells (imDCs) play an important role in the induction of donor-specific transplant immunotolerance. However, these cells have limitations, such as rapid maturation and a short lifespan in vivo . In previous studies, induced pluripotent stem cells (iPSCs) differentiated into imDCs, and sinomenine (SN) was used to inhibit the maturation of imDCs. AIM To study the capacity of SN to maintain iPSC-derived imDCs (SN-iPSCs-imDCs) in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance. METHODS In this study, mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN (iPSCs-imDCs and SN-iPSCs-imDCs). The imDC-related surface markers, endocytotic capacity of fluorescein isothiocyanate-Dextran and apoptosis were analyzed by flow cytometry. The effects of iPSCs-imDCs and SN-iPSCs-imDCs on T-cell stimulatory function, and regulatory T (Treg) cell proliferative function in vitro were analyzed by mixed lymphocyte reaction. Cytokine expression was detected by ELISA. The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting. The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice. Statistical evaluation of graft survival was performed using Kaplan–Meier curves. RESULTS Both iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained, and their biological characteristics and ability to induce immunotolerance were compared. SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs. Reduced major histocompatibility complex II expression, worse T-cell stimulatory function, higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs ( P < 0.05). The levels of interleukin (IL)-2, IL-12, interferon-γ in SN-iPSCs-imDCs were lower than those in iPSCs-imDCs, whereas IL-10 and transforming growth factor-β levels were higher ( P < 0.05). The apoptosis rate of these cells was significantly higher ( P < 0.05), and the expression levels of cleaved caspase3, Bax and cleaved poly(ADP-ribose) polymerase were higher after treatment with lipopolysaccharides, but Bcl-2 was reduced. In Balb/c mice recipients immunized with iPSCs-imDCs or SN-iPSCs-imDCs 7 d before skin grafting, the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4 + T-cell proliferation ( P < 0.05) and a higher capacity to induce CD4 + CD25 + FoxP3 + Treg cell proliferation in the spleen ( P < 0.05). The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a do...

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Cyclosporine A, in Contrast to Rapamycin, Affects the Ability of Dendritic Cells to Induce Immune Tolerance Mechanisms

Cited by 3 publications

References 74 publications

Heterogeneity of adherent and non‑adherent JAWS II dendritic cells

Heterogeneity of adherent and non‑adherent JAWS II dendritic cells

Dendritic Cells: A Bridge between Tolerance Induction and Cancer Development in Transplantation Setting

Sinomenine promotes differentiation of induced pluripotent stem cells into immature dendritic cells with high induction of immune tolerance

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