Despite recent progress in the treatment of rheumatoid arthritis (RA), many patients still fail to achieve remission or low disease activity. An imbalance between auto-reactive effector T cells (Teff) and regulatory T cells (Treg) may contribute to joint inflammation and damage in RA. Therefore, restoring this balance is a promising approach for the treatment of inflammatory arthritis. Accordingly, our group has previously shown that the combination of TGF-β-releasing microparticles (MP), rapamycin-releasing MP, and IL-2-releasing MP (TRI MP) can effectively increase the ratio of Tregs to Teff in vivo and provide disease protection in several preclinical models. In this study TRI MP was evaluated in the collagen-induced arthritis (CIA) model. Although this formulation has been tested previously in models of destructive inflammation and transplantation, this is the first model of autoimmunity for which this therapy has been applied. In this context, TRI MP effectively reduced arthritis incidence, the severity of arthritis scores, and bone erosion. The proposed mechanism of action includes not only reducing CD4⁺ T cell proliferation, but also expanding a regulatory population in the periphery soon after TRI MP administration. These changes were reflected in the CD4⁺ T cell population that infiltrated the paws at the onset of arthritis and were associated with a reduction of immune infiltrate and inflammatory myeloid cells in the paws. TRI MP administration also reduced the titer of collagen antibodies, however the contribution of this reduced titer to disease protection remains uncertain since there was no correlation between collagen antibody titer and arthritis score.

尽管最近在类风湿性关节炎（RA）的治疗方面取得了进展，但许多患者仍未能获得缓解或疾病活动率低。自身反应性效应T细胞（Teff）和调节性T细胞（Treg）之间的失衡可能导致RA的关节发炎和损伤。因此，恢复这种平衡是治疗炎性关节炎的有前途的方法。因此，我们的研究小组先前表明，TGF-β释放微粒（MP），雷帕霉素释放MP和IL-2释放MP（TRI MP）的组合可以有效提高体内Treg与Teff的比率并在几种临床前模型中提供疾病保护。在这项研究中，TRI MP在胶原诱导的关节炎（CIA）模型中进行了评估。尽管此制剂先前已在破坏性炎症和移植模型中进行过测试，但这是应用该疗法的首个自身免疫模型。在这种情况下，TRI MP有效降低了关节炎的发生率，关节炎评分的严重性和骨侵蚀。拟议的作用机制不仅包括减少CD4 ⁺ T细胞的增殖，而且还包括在TRI MP给药后不久在外周扩大调节人群。这些变化反映在CD4 ⁺在关节炎发作时渗透到爪中的T细胞群与爪中免疫浸润和炎性髓样细胞的减少有关。TRI MP给药也降低了胶原蛋白抗体的效价，但是这种降低的效价对疾病保护的贡献仍然不确定，因为胶原蛋白抗体效价与关节炎评分之间没有相关性。