biostudies-literatureMcBride DANIDCR NIH HHSNCATS NIH HHSNIAID NIH HHSNHLBI NIH HHSNCI NIH HHSNational Institutes of HealthNIAMS NIH HHSNIH HHSNational Science Foundatione2202720https://www.ebi.ac.uk/biostudies/studies/S-EPMC10104670biostudies-literatureUnknown10(11)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 encapsulatiAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis.PMC10104670R01 AI148073UL1TR001442S10 OD025052F31AR079921(D.A.M.)F31 AR079921UL1 TR001442R03DE031009(N.J.S)R01 AR065466T32AR064194R01AI148073(N.B.)S10OD025052T32CA153915P30AR073761(N.B.)R03 DE031009P30 AR073761P30CA23100T32 AR064194P30 CA023100ECCS‐2025752T32 CA153915F31 HL164055F31HL164055(M.D.K.)Svensson MNDBottini NShah NJDorn NCMcBride DAYao MPrideaux EBKerr MDNguyen AWang WJohnson WTZoccheddu MfalseImmunomodulatory 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 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 encapsulati2023-01-01T00:00:00Z2023 Apr2025-04-04T23:00:59.362Z2025-04-04T23:00:59.362ZS-EPMC101046703689065710.1002/advs.202202720