Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells.
Induced T regulatory cells suppress osteoclastogenesis and bone erosion in collagen-induced arthritis better than natural T regulatory cells.
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诱导 T 调节细胞比天然 T 调节细胞更好地抑制胶原诱导的关节炎中的破骨细胞生成和骨侵蚀。
DOI：
10.1136/annrheumdis-2011-201052
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发表时间：
2012-09
影响因子：
27.4
通讯作者：
Zheng SG
中科院分区：
文献类型：
--
作者：
Kong N;Lan Q;Su W;Chen M;Wang J;Yang Z;Park R;Dagliyan G;Conti PS;Brand D;Liu Z;Stohl W;Zou H;Zheng SG
破骨细胞是类风湿性关节炎（RA）中骨破坏的主要原因，而天然CD 4 + Foxp 3+调节性T细胞（nTcells）可抑制破骨细胞的生成。本研究旨在确定TGF-β诱导的CD 4 + Foxp 3+调节性T细胞（iTCLs）是否也抑制胶原诱导的关节炎（CIA）中的成骨细胞生成和骨侵蚀。用RANKL和巨噬细胞集落刺激因子（M-CSF）从骨髓CD 11b+细胞中诱导破骨细胞，并用抗酒石酸酸性磷酸酶（TRAP）染色进行评估。用TGF-β产生CD 4 + iT细胞，并以不同比例加入到具有CD 11b+细胞的培养物中。进行Transwell和抗体阻断实验以确定作用机制。通过蛋白质印迹法测定NF-κ B活化。在用CII/CFA免疫后第14天，将3×106个CD 4 + iT细胞、nT细胞或对照细胞过继转移至DBA 1/J小鼠。监测CIA的发病和严重程度，并通过CT扫描检查骨质侵蚀。两种CD 4 + T细胞几乎完全抑制破骨细胞生成，但在体外IL-6存在下，只有iT细胞维持这种作用。在免疫后和CIA发作前注射的CD 4 + iT细胞而非nT细胞和对照细胞显著抑制疾病发展。值得注意的是，CT扫描显示，CD 4 + iT细胞而非nT细胞或对照细胞输注的CIA中的关节具有较少的骨侵蚀。用CD 4 + iT细胞而不是其他细胞处理显著降低体外破骨细胞中NF-κ B p65/p50的水平和体内滑膜组织中P65/50和RANKL的表达。CD 4 + iT细胞的调控可能对类风湿关节炎及其他骨侵蚀相关疾病有治疗作用。
Osteoclasts are responsible for bone destruction in rheumatoid arthritis (RA) and natural CD4+Foxp3+regulatory T cells (nTregs) can inhibit osteoclastogenesis. This study aims to determine whether TGF-β-induced CD4+Foxp3+regulatory T cells (iTregs) also suppress osteolastogenesis and bone erosion in collagen induced arthritis (CIA). Osteoclasts were induced from bone-marrow CD11b+ cells with RANKL and macrophage colony-stimulating factor (M-CSF), and assessed with tartrate-resistant acid phosphatase (TRAP) staining. CD4+ iTregs were generated with TGF-β and added to cultures with different ratios with CD11b+ cells. Transwell and antibody blockade experiments were performed to define the mechanism of action. NF-kB activation was determined by western blot. 3×106 CD4+ iTregs, nTregs or control cells were adoptively transferred to DBA1/J mice on day 14 after immunization with CII/CFA. CIA onset and severity were monitored and bone erosion was examined by CT scan. Both CD4+ Tregs almost completely suppressed osteoclastogenesis but only iTregs sustained the effect in the presence of IL-6 in vitro. CD4+ iTregs but not nTregs and control cells injected after immunization and before of onset of CIA significantly suppressed disease development. Of note, CT scan showed that the joints in CD4+ iTregs but not nTregs or control cells infused CIA had less bone erosion. Treatment with CD4+ iTregs but not other cells dramatically decreased the levels of NF-kB p65/p50 in osteoclasts in vitro and P65/50 and RANKL expression by synovial tissues in vivo. Manipulation of CD4+ iTregs may have therapeutic effects on rheumatoid arthritis and other bone erosion related diseases.
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影响因子：
--
作者：
Zaiss, Mario M.;Axmann, Roland;Schett, Georg
通讯作者：
Schett, Georg
尖端技术：全反式视黄酸维持炎症环境中天然调节性 T 细胞的稳定性和功能
DOI：
10.4049/jimmunol.1000598
发表时间：
2010-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zhou X;Kong N;Wang J;Fan H;Zou H;Horwitz D;Brand D;Liu Z;Zheng SG
通讯作者：
Zheng SG
影响因子：
27.4
作者：
Kremer, Joel M.;Russell, Anthony S.;Genant, Harry K.
通讯作者：
Genant, Harry K.
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
3.5
作者：
Zhou X;Kong N;Zou H;Brand D;Li X;Liu Z;Zheng SG
通讯作者：
Zheng SG