Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis

McBride, D. A. (author)

Kerr, M. D. (author)

Johnson, W. T. (author)

Nguyen, Anders, 1995 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research

Zoccheddu, M. (author)

Yao, M. N. (author)

Prideaux, E. B. (author)

Dorn, N. C. (author)

Wang, W. (author)

Svensson, Mattias N D (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research

Bottini, N. (author)

Shah, N. J. (author)

(creator_code:org_t)

Related links:: https://gup.ub.gu.se...; show more...; https://doi.org/10.1...; show less...

Abstract Subject headings

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 naive 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.

By the author/editor: McBride, D. A.; Kerr, M. D.; Johnson, W. T.; Nguyen, Anders, ...; Zoccheddu, M.; Yao, M. N.; show more...; Prideaux, E. B.; Dorn, N. C.; Wang, W.; Svensson, Mattia ...; Bottini, N.; Shah, N. J.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

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