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Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells

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...

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Autores principales: Colombo, Miriam, Marongiu, Laura, Mingozzi, Francesca, Marzi, Roberta, Cigni, Clara, Facchini, Fabio Alessandro, Rotem, Rany, Valache, Mihai, Stucchi, Giulia, Rocca, Giuseppe, Gornati, Laura, Rizzuto, Maria Antonietta, Salvioni, Lucia, Zanoni, Ivan, Gori, Alessandro, Prosperi, Davide, Granucci, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482116/
https://www.ncbi.nlm.nih.gov/pubmed/36124235
http://dx.doi.org/10.1016/j.isci.2022.105042
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author Colombo, Miriam
Marongiu, Laura
Mingozzi, Francesca
Marzi, Roberta
Cigni, Clara
Facchini, Fabio Alessandro
Rotem, Rany
Valache, Mihai
Stucchi, Giulia
Rocca, Giuseppe
Gornati, Laura
Rizzuto, Maria Antonietta
Salvioni, Lucia
Zanoni, Ivan
Gori, Alessandro
Prosperi, Davide
Granucci, Francesca
author_facet Colombo, Miriam
Marongiu, Laura
Mingozzi, Francesca
Marzi, Roberta
Cigni, Clara
Facchini, Fabio Alessandro
Rotem, Rany
Valache, Mihai
Stucchi, Giulia
Rocca, Giuseppe
Gornati, Laura
Rizzuto, Maria Antonietta
Salvioni, Lucia
Zanoni, Ivan
Gori, Alessandro
Prosperi, Davide
Granucci, Francesca
author_sort Colombo, Miriam
collection PubMed
description 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.
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spelling pubmed-94821162022-09-18 Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells Colombo, Miriam Marongiu, Laura Mingozzi, Francesca Marzi, Roberta Cigni, Clara Facchini, Fabio Alessandro Rotem, Rany Valache, Mihai Stucchi, Giulia Rocca, Giuseppe Gornati, Laura Rizzuto, Maria Antonietta Salvioni, Lucia Zanoni, Ivan Gori, Alessandro Prosperi, Davide Granucci, Francesca iScience Article 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. Elsevier 2022-08-30 /pmc/articles/PMC9482116/ /pubmed/36124235 http://dx.doi.org/10.1016/j.isci.2022.105042 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Colombo, Miriam
Marongiu, Laura
Mingozzi, Francesca
Marzi, Roberta
Cigni, Clara
Facchini, Fabio Alessandro
Rotem, Rany
Valache, Mihai
Stucchi, Giulia
Rocca, Giuseppe
Gornati, Laura
Rizzuto, Maria Antonietta
Salvioni, Lucia
Zanoni, Ivan
Gori, Alessandro
Prosperi, Davide
Granucci, Francesca
Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
title Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
title_full Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
title_fullStr Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
title_full_unstemmed Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
title_short Specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
title_sort specific immunosuppressive role of nanodrugs targeting calcineurin in innate myeloid cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482116/
https://www.ncbi.nlm.nih.gov/pubmed/36124235
http://dx.doi.org/10.1016/j.isci.2022.105042
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