Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis.
Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis.
复制标题
单核细胞 MDSC 使 Th17 细胞偏向促破骨细胞表型，并增强类风湿性关节炎的骨侵蚀。
DOI：
10.1093/rheumatology/keaa625
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发表时间：
2021-05-14
期刊：
影响因子：
--
通讯作者：
Wang XY
中科院分区：
文献类型：
--
作者：
Chen S;Guo C;Wang R;Feng Z;Liu Z;Wu L;Zhao D;Zheng S;Chen F;Zhang D;Xu J;Zhu J;Chen X;Li Z;Wise CM;Li J;Wang XY
目标
虽然骨髓源性抑制细胞（MDSC）先前显示在自身免疫性疾病中促进促炎性辅助性T细胞（Th）17应答，但MDSC-Th 17免疫轴对RA异常骨破坏的潜在影响在很大程度上仍然未知。
方法
我们研究了类风湿关节炎患者MDSC或其亚群的频率与关节破坏之间的相关性。患者来源的MDSC和Th 17细胞的相互作用进行了研究，在体外破骨细胞（OC）分化和骨吸收测定，这是进一步验证使用小鼠模型的RA。通过MDSC的消耗或转移来确定MDSC对体内破骨细胞生成和骨侵蚀的贡献。
结果
人MDSC，特别是单核细胞MDSC（M-MDSC），表现出固有的OC分化能力，并与RA患者的临床骨侵蚀呈正相关。引人注目的是，患者来源的M-MDSC可以将Th 17细胞编程为促破骨细胞生成表型，这反过来通过核因子κ B受体激活剂配体（RANK-L）-RANK信号传导增强OC分化。使用RA小鼠模型进一步证实了由M-MDSC和Th 17细胞的相互作用驱动的这种增强的骨质溶解。M-MDSC的选择性耗竭显著改善关节炎小鼠中的破骨细胞生成和疾病严重程度，而M-MDSC的转移减轻了与受体小鼠中OC增加相关的骨侵蚀。
结论
我们的研究结果突出了MDSC的功能可塑性，并确定了一种新的前破骨细胞生成途径，由骨髓细胞和T淋巴细胞之间的相互作用在自身免疫性RA。
OBJECTIVES
While myeloid-derived suppressor cells (MDSCs) were previously shown to promote a proinflammatory T helper (Th) 17 response in autoimmune conditions, a potential impact of the MDSC-Th17 immune axis on abnormal bone destruction in RA remains largely unknown.
METHODS
We investigated the correlation between the frequency of MDSCs or its subsets and joint destruction in RA patients. The reciprocal actions of patient-derived MDSCs and Th17 cells were studied using osteoclast (OC) differentiation and bone resorption assays in vitro, which were further validated using mouse models of RA. Contribution of MDSCs to osteoclastogenesis and bone erosion in vivo was determined by depletion or transfer of MDSCs.
RESULTS
Human MDSCs, particularly monocytic MDSCs (M-MDSCs), exhibit inherent OC-differentiating capacity and positively correlate with clinical bone erosion in RA patients. Strikingly, patient-derived M-MDSCs can program Th17 cells towards a pro-osteoclastogenic phenotype, which in return potentiates OC differentiation via the receptor activator of nuclear factor κΒ ligand (RANK-L)-RANK signalling. This enhanced osteolysis driven by the reciprocal actions of M-MDSCs and Th17 cells is further confirmed using mouse models of RA. Selective depletion of M-MDSCs significantly ameliorates osteoclastogenesis and disease severity in arthritic mice, whereas transfer of M-MDSCs aggravates bone erosion associated with increased OCs in recipient mice.
CONCLUSION
Our findings highlight the functional plasticity of MDSCs and identify a novel pro-osteoclastogenic pathway governed by interplay between myeloid cells and T lymphocytes in autoimmune RA.
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DOI：
10.1084/jem.20061775
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sato K;Suematsu A;Okamoto K;Yamaguchi A;Morishita Y;Kadono Y;Tanaka S;Kodama T;Akira S;Iwakura Y;Cua DJ;Takayanagi H
通讯作者：
Takayanagi H
影响因子：
64.8
作者：
Sakaguchi, N;Takahashi, T;Sakaguchi, S
通讯作者：
Sakaguchi, S
影响因子：
11.2
作者：
Sawant A;Deshane J;Jules J;Lee CM;Harris BA;Feng X;Ponnazhagan S
通讯作者：
Ponnazhagan S
类风湿关节炎中掌pophopophanegeal和近端指间关节的超声检查：与磁共振成像，常规放射线照相和临床检查的比较。
影响因子：
4.9
作者：
Szkudlarek, Marcin;Klarlund, Mette;Narvestad, Eva;Court-Payen, Michel;Strandberg, Charlotte;Jensen, Karl E.;Thomsen, Henrik S.;Ostergaard, Mikkel
通讯作者：
Ostergaard, Mikkel
影响因子：
16.6
作者：
Bronte V;Brandau S;Chen SH;Colombo MP;Frey AB;Greten TF;Mandruzzato S;Murray PJ;Ochoa A;Ostrand-Rosenberg S;Rodriguez PC;Sica A;Umansky V;Vonderheide RH;Gabrilovich DI
通讯作者：
Gabrilovich DI