2023-04-04 カリフォルニア大学サンディエゴ校(UCSD)
ATRA(オールトランスレチノイン酸)と呼ばれる物質を人工的に放出することで、疾患を引き起こす細胞を規制性T細胞と呼ばれる細胞に変え、体内で他の部位で疾患を治療できるようにする。ATRAを高分子材料でカプセル化し、治療的濃度で関節内に直接注入することで、従来よりも制御された放出が可能になった。
この研究は、Advanced Science誌2023年3月8日号に掲載された。
<関連情報>
- https://today.ucsd.edu/story/biodegradable-polymer-system-offers-new-hope-for-treating-rheumatoid-arthritis
- https://onlinelibrary.wiley.com/doi/10.1002/advs.202202720
免疫調節マイクロパーティクルはT細胞をエピジェネティックに修飾し、全身的に自己免疫性関節炎を改善する Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis
David A. McBride, Matthew D. Kerr, Wade T. Johnson, Anders Nguyen, Martina Zoccheddu, Mina Yao, Edward B. Prideaux, Nicholas C. Dorn, Wei Wang, Mattias N.D. Svensson, Nunzio Bottini, Nisarg J. Shah
Advanced Science Published: 08 March 2023
DOI:https://doi.org/10.1002/advs.202202720
Abstract
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 (Treg) and suppression of Treg 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 Treg which in turn reduce inflammation and modify disease in injected and uninjected joints, a phenotype that is also reproduced by IA injection of Treg. 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.
