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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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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. |
format | Online Article Text |
id | pubmed-9482116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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