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Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis

Disease modifying antirheumatic drugs (DMARDs) have improved the prognosis of autoimmune inflammatory arthritides but a large fraction of patients display partial or nonresponsiveness to front‐line DMARDs. Here, an immunoregulatory approach based on sustained joint‐localized release of all‐trans ret...

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Autores principales: McBride, David A., Kerr, Matthew D., Johnson, Wade T., Nguyen, Anders, Zoccheddu, Martina, Yao, Mina, Prideaux, Edward B., Dorn, Nicholas C., Wang, Wei, Svensson, Mattias N.D., Bottini, Nunzio, Shah, Nisarg J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104670/
https://www.ncbi.nlm.nih.gov/pubmed/36890657
http://dx.doi.org/10.1002/advs.202202720
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author McBride, David A.
Kerr, Matthew D.
Johnson, Wade T.
Nguyen, Anders
Zoccheddu, Martina
Yao, Mina
Prideaux, Edward B.
Dorn, Nicholas C.
Wang, Wei
Svensson, Mattias N.D.
Bottini, Nunzio
Shah, Nisarg J.
author_facet McBride, David A.
Kerr, Matthew D.
Johnson, Wade T.
Nguyen, Anders
Zoccheddu, Martina
Yao, Mina
Prideaux, Edward B.
Dorn, Nicholas C.
Wang, Wei
Svensson, Mattias N.D.
Bottini, Nunzio
Shah, Nisarg J.
author_sort McBride, David A.
collection PubMed
description Disease modifying antirheumatic drugs (DMARDs) have improved the prognosis of autoimmune inflammatory arthritides but a large fraction of patients display partial or nonresponsiveness to front‐line DMARDs. Here, an immunoregulatory approach based on sustained joint‐localized release of all‐trans retinoic acid (ATRA), which modulates local immune activation and enhances disease‐protective T cells and leads to systemic disease control is reported. ATRA imprints a unique chromatin landscape in T cells, which is associated with an enhancement in the differentiation of naïve T cells into anti‐inflammatory regulatory T cells (T(reg)) and suppression of T(reg) destabilization. Sustained release poly‐(lactic‐co‐glycolic) acid (PLGA)‐based biodegradable microparticles encapsulating ATRA (PLGA‐ATRA MP) are retained in arthritic mouse joints after intra‐articular (IA) injection. IA PLGA‐ATRA MP enhance migratory T(reg) which in turn reduce inflammation and modify disease in injected and uninjected joints, a phenotype that is also reproduced by IA injection of T(reg). PLGA‐ATRA MP reduce proteoglycan loss and bone erosions in the SKG and collagen‐induced arthritis mouse models of autoimmune arthritis. Strikingly, systemic disease modulation by PLGA‐ATRA MP is not associated with generalized immune suppression. PLGA‐ATRA MP have the potential to be developed as a disease modifying agent for autoimmune arthritis.
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spelling pubmed-101046702023-04-15 Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis McBride, David A. Kerr, Matthew D. Johnson, Wade T. Nguyen, Anders Zoccheddu, Martina Yao, Mina Prideaux, Edward B. Dorn, Nicholas C. Wang, Wei Svensson, Mattias N.D. Bottini, Nunzio Shah, Nisarg J. Adv Sci (Weinh) Research Articles Disease modifying antirheumatic drugs (DMARDs) have improved the prognosis of autoimmune inflammatory arthritides but a large fraction of patients display partial or nonresponsiveness to front‐line DMARDs. Here, an immunoregulatory approach based on sustained joint‐localized release of all‐trans retinoic acid (ATRA), which modulates local immune activation and enhances disease‐protective T cells and leads to systemic disease control is reported. ATRA imprints a unique chromatin landscape in T cells, which is associated with an enhancement in the differentiation of naïve T cells into anti‐inflammatory regulatory T cells (T(reg)) and suppression of T(reg) destabilization. Sustained release poly‐(lactic‐co‐glycolic) acid (PLGA)‐based biodegradable microparticles encapsulating ATRA (PLGA‐ATRA MP) are retained in arthritic mouse joints after intra‐articular (IA) injection. IA PLGA‐ATRA MP enhance migratory T(reg) which in turn reduce inflammation and modify disease in injected and uninjected joints, a phenotype that is also reproduced by IA injection of T(reg). PLGA‐ATRA MP reduce proteoglycan loss and bone erosions in the SKG and collagen‐induced arthritis mouse models of autoimmune arthritis. Strikingly, systemic disease modulation by PLGA‐ATRA MP is not associated with generalized immune suppression. PLGA‐ATRA MP have the potential to be developed as a disease modifying agent for autoimmune arthritis. John Wiley and Sons Inc. 2023-03-08 /pmc/articles/PMC10104670/ /pubmed/36890657 http://dx.doi.org/10.1002/advs.202202720 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
McBride, David A.
Kerr, Matthew D.
Johnson, Wade T.
Nguyen, Anders
Zoccheddu, Martina
Yao, Mina
Prideaux, Edward B.
Dorn, Nicholas C.
Wang, Wei
Svensson, Mattias N.D.
Bottini, Nunzio
Shah, Nisarg J.
Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
title Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
title_full Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
title_fullStr Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
title_full_unstemmed Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
title_short Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
title_sort immunomodulatory microparticles epigenetically modulate t cells and systemically ameliorate autoimmune arthritis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104670/
https://www.ncbi.nlm.nih.gov/pubmed/36890657
http://dx.doi.org/10.1002/advs.202202720
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