Harnessing the dual immunomodulatory function of myeloid-derived suppressor cells to reshape the inflammatory microenvironment for osteoarthritis therapy

作者：Zili Guo, Tao Chen, Xuehuan Wen, Qiangchang Fu, Jiabin Lai, Jiajin Li, Jiayu Chen, Jie Weng, Wen Wang, Qihua Cao, Junxiong Zhu, Zhaoming Ye, Xiao-Hua Yu, Lifeng Jiang · 发表于：Materials Today Bio · 年份：2025 · DOI：10.1016/j.mtbio.2025.102332 · 被引用次数：3 · 研究领域：Immune cells in cancer、Immune Response and Inflammation、Inflammation biomarkers and pathways

Osteoarthritis (OA) pathogenesis is profoundly influenced by dysregulated immune dynamics, where persistent interleukin-17 (IL-17)/T helper 17 (Th17) cell mediated inflammation coordinates with failed regenerative processes to perpetuate joint destruction. Here, we unveil the role of myeloid-derived suppressor cells (MDSCs) as dual-phase regulators that paradoxically orchestrate both inflammatory escalation and tissue repair in OA progression. Intra-articular administration of MDSCs in OA mice amplified IL-17 dependent inflammatory cascades and chemokine-driven leukocyte recruitment, revealing a context-dependent pro-inflammatory phenotype. Unexpectedly, MDSC depletion failed to attenuate joint damage, implying their indispensable yet multifaceted role in OA pathogenesis. Mechanistically, MDSCs exhibited functional plasticity by upregulating arginase-1 to polarize M2 macrophages, fostering a regenerative niche alongside their inflammatory activity. To resolve this duality, we developed a bio-responsive hydrogel-microsphere system integrating transforming growth factor β1 (TGF-β1) and interleukin-1 β1 antibody (anti-IL-1β) loaded mesoporous silica nanoparticles (MSNs). This spatiotemporally controlled platform selectively suppressed MDSC-mediated Th17 cell expansion while harnessing their intrinsic capacity to drive M2 macrophage polarization and chondrogenesis. The resultant shift from a pro-inflammatory to pro-regenerative microenvironment significantly attenuated cartilage ...