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Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells

ABSTRACT: Summary Calcineurin (CN) inhibitors currently used to avoid transplant rejection block the activation of adaptive immune responses but also prevent the development of tolerance toward the graft, by directly inhibiting T cells. CN, through the transcription factors of the NFAT family, plays an important role also in the differentiation dendritic cells (DCs), the main cells responsible for the activation of T lymphocytes. Therefore, we hypothesized that the inhibition of CN only in DCs and not in T cells could be sufficient to prevent T cell responses, while allowing for the development of tolerance. Here, we show that inhibition of CN/NFAT pathway in innate myeloid cells, using a new nanoconjugate capable of selectively targeting phagocytes in vivo, protects against graft rejection and induces a longer graft acceptance compared to common CN inhibitors. We propose a new generation of nanoparticles-based selective immune suppressive agents for a better control of transplant acceptance. Graphical abstract Highlights • Calcineurin/NFATc2 pathway is required to enable DC migration to draining lymph nodes• Calcineurin/NFATc2 pathway in DCs is required for type I immune responses activation• Superparamagnetic iron oxide NPs can be used to efficiently target phagocytes in vivo• Specific delivery of calcineurin inhibitor by NPs to phagocytes induce graft acceptance Health sciences; Drugs; Immunology; Immune response

SUBMITTER: Colombo M

PROVIDER: S-EPMC9482116 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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