Recruited CD68(+)CD206(+) macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration.
Recruited CD68(+)CD206(+) macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration.
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招募的CD68( )CD206( )-巨噬细胞协调移植物免疫耐受以促进基于异种牙本质基质的牙根再生
DOI：
10.1016/j.bioactmat.2020.09.029
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发表时间：
2021-04
影响因子：
18.9
通讯作者：
Tian W
中科院分区：
文献类型：
--
作者：
Li H;Sun J;Yang H;Han X;Luo X;Liao L;Yang B;Zhu T;Huo F;Guo W;Tian W
异种细胞外基质的成功再生医学策略需要炎症、纤维化和重塑过程之间的协同平衡。适应性巨噬细胞亚群已被确定可以调节炎症并协调邻近实质组织的修复。本研究构建了PPARγ引发的CD68+CD206+ M2表型（M2γ），并首次验证了其在异种生物工程器官再生中的抗炎和组织再生作用。我们的结果表明，Th1 型 CD3+CD8+ T 细胞对基于异种牙本质基质的生物工程根复合物（xeno-complex）的反应在体外被 M2γ 巨噬细胞显着抑制。 PPARγ激活还及时招募CD68+CD206+组织巨噬细胞极化至体内异种复合物。这些子集减轻了炎症部位的促炎细胞因子（TNF-α、IFN-γ），并减少了外周系统中的 CD3+CD8+ T 淋巴细胞。当转化为原位非人灵长类动物模型时，PPARγ引发的M2巨噬细胞免疫抑制IL-1β、IL-6、TNF-α、MMP，使异种复合物能够有效逃避免疫介导的排斥反应并启动移植物-宿主协同完整性。这些集体活动促进了成牙本质细胞样和牙周样细胞的分化，以引导牙髓-牙本质和牙骨质-PDLs-骨再生，并挽救部分受损的牙发育，例如DSPP和骨膜素表达。最后，再生牙根在结构、生物力学和功能上与原生牙相当。 M1巨噬细胞向M2巨噬细胞的及时转化主要协调成牙、纤维发生和成骨，这代表了靶器官完整实质间质组织再生的潜在调节剂。替代的极化 M2 巨噬细胞可以发挥抗炎作用，抑制异种宿主移植排斥。使用生物工程牙根再生模型来研究实质/硬组织和基质/软组织再生。 PPARγ 引发的 M2 巨噬细胞协调移植物免疫耐受，促进牙生成、纤维生成和骨生成。
Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation, fibrosis, and remodeling process. Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues. This study fabricated PPARγ-primed CD68+CD206+ M2 phenotype (M2γ), and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration. Our results showed that Th1-type CD3+CD8+ T cell response to xenogeneic-dentin matrix-based bioengineered root complex (xeno-complex) was significantly inhibited by M2γ macrophage in vitro. PPARγ activation also timely recruited CD68+CD206+ tissue macrophage polarization to xeno-complex in vivo. These subsets alleviated proinflammatory cytokines (TNF-α, IFN-γ) at the inflammation site and decreased CD3+CD8+ T lymphocytes in the periphery system. When translated to an orthotopic nonhuman primate model, PPARγ-primed M2 macrophages immunosuppressed IL-1β, IL-6, TNF-α, MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity. These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression. Finally, the regenerated root showed structure-biomechanical and functional equivalency to the native tooth. The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis, fibrogenesis, and osteogenesis, which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs. Alternative polarized M2 macrophage could perform anti-inflammatory effects to inhibit xenogeneic host-to-graft rejection. A model of bioengineered tooth root regeneration was used to study parenchymal/hard and stromal/soft tissues regeneration. PPARγ-primed M2 macrophage orchestrated graft immune tolerance to prompt odontogenesis, fibrogenesis, and osteogenesis.
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影响因子：
64.8
作者：
Karin M;Clevers H
通讯作者：
Clevers H
影响因子：
7.8
作者：
Huleihel L;Dziki JL;Bartolacci JG;Rausch T;Scarritt ME;Cramer MC;Vorobyov T;LoPresti ST;Swineheart IT;White LJ;Brown BN;Badylak SF
通讯作者：
Badylak SF
影响因子：
3.1
作者：
Chaussain C;Eapen AS;Huet E;Floris C;Ravindran S;Hao J;Menashi S;George A
通讯作者：
George A
DOI：
10.1038/nrm3176
发表时间：
2011-08-23
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia