Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.

Autor: McBride DA; Department of Nanoengineering, University of California, La Jolla, San Diego, CA, 92093, USA.; Chemical Engineering Program, University of California, La Jolla, San Diego, CA, 92093, USA., Kerr MD; Department of Nanoengineering, University of California, La Jolla, San Diego, CA, 92093, USA.; Chemical Engineering Program, University of California, La Jolla, San Diego, CA, 92093, USA., Johnson WT; Department of Nanoengineering, University of California, La Jolla, San Diego, CA, 92093, USA., Nguyen A; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, 41346, Sweden., Zoccheddu M; Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, La Jolla, San Diego, CA, 92093, USA., Yao M; Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, CA, 92093, USA., Prideaux EB; Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, CA, 92093, USA., Dorn NC; Department of Nanoengineering, University of California, La Jolla, San Diego, CA, 92093, USA.; Chemical Engineering Program, University of California, La Jolla, San Diego, CA, 92093, USA., Wang W; Department of Chemistry and Biochemistry, University of California, La Jolla, San Diego, CA, 92093, USA.; Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA, 92093, USA., Svensson MND; Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, 41346, Sweden., Bottini N; Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California, La Jolla, San Diego, CA, 92093, USA., Shah NJ; Department of Nanoengineering, University of California, La Jolla, San Diego, CA, 92093, USA.; Chemical Engineering Program, University of California, La Jolla, San Diego, CA, 92093, USA.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2023 Apr; Vol. 10 (11), pp. e2202720. Date of Electronic Publication: 2023 Mar 08.
DOI: 10.1002/advs.202202720
Abstrakt: 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.
(© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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