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T cell-depleting nanoparticles ameliorate bone loss by reducing activated T cells and regulating the Treg/Th17 balance

引用

Bioactive Materials 2021年第10期6卷 3150-3163页

作者： Xiaoshan Yang Fuxing Zhou Pingyun Yuan Geng Dou Xuemei Liu Siying Liu Xiangdong Wang Ronghua Jin Yan Dong Jun Zhou Yajie Lv Zhihong Deng Shiyu Liu Xin Chen Ying Han Yan Jin State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi International Joint Research Center for Oral Diseases Center for Tissue EngineeringSchool of StomatologyFourth Military Medical UniversityXi’anShaanxi710032China Xijing Hospital of Digestive Diseases&State Key Laboratory of Cancer Biology Fourth Military Medical UniversityXi’anShaanxi710032China Department of Gynecology and Obstetrics Xijing HospitalFourth Military Medical UniversityXi’anShaanxi710032China School of Chemical Engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationInstitute of Polymer Science in Chemical EngineeringXi’an Jiao Tong UniversityXi’anShaanxi710049China Department of Dermatology Tangdu HospitalFourth Military Medical UniversityXi’anShaanxi710038China

Estrogen deficiency is one of the most frequent causes of osteoporosis in postmenopausal *** chronic inflammatory conditions caused by estrogen deficiency,activated T cells contribute to elevated levels of proinflammatory cytokines,impaired osteogenic differentiation capabilities of bone marrow mesenchymal stem cells(BMMSCs),and disturbed regulatory T cell(Treg)/Th17 cell ***,therapeutic strategies that re-establish immune homeostasis in this disorder have not been well ***,we produced T cell-depleting nanoparticles(TDNs)that ameliorated the osteopenia phenotype and rescued the osteogenic deficiency of BMMSCs in ovariectomized(OVX)*** consist of monocyte chemotactic protein-1(MCP-1)-encapsulated mesoporous silica nanoparticles as the core and Fas-ligand(FasL)as the *** showed that the delicate design of the TDNs enables rapid release of MCP-1 to recruit activated T cells and then induces their apoptosis through the conjugated FasL both in vitro and in *** signals recognized by macrophages help skew the Treg/Th17 cell balance and create an immune tolerant state,further attenuating the osteogenic deficiency of BMMSCs and the osteopenia ***,we found that the therapeutic effects of TDNs were partially mediated by apoptotic T cell-derived extracellular vesicles(ApoEVs),which promoted macrophage transformation towards the M2 *** findings demonstrate that TDNs may represent a promising strategy for treating osteoporosis and other immune disorders.

关键词： Nanoparticles Activated T cell Immune tolerance apoptotic extracellular vesicles Osteoporosis

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