Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice.
Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice.
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DOI：
10.1186/s13075-023-03133-4
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发表时间：
2023-08-09
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
--
作者：
Tau蛋白在神经炎症中起促炎作用。然而，tau在类风湿性关节炎(RA)等其他炎症性疾病中的作用却鲜有人研究。本研究旨在探讨内源性tau在炎性关节炎发病机制中的作用及其可能机制。我们在野生型和Tau-/-小鼠上建立了胶原诱导性关节炎(CIA)模型，比较了两种动物的临床评分和关节炎发生率。用Micro-CT分析评价踝关节的骨侵蚀情况。进行组织学分析，评估踝关节的炎性细胞浸润、软骨损伤和破骨细胞活性。采用双抗体夹心法测定血清促炎细胞因子水平。免疫组织化学染色和实时定量聚合酶链式反应检测巨噬细胞标志物的表达水平。在炎症状态下，Tau在关节中表达上调。Tau缺失的小鼠表现出较温和的炎症，并可防止CIA的进展，证据是血清促炎细胞因子水平降低，踝关节骨丢失、炎症细胞浸润、软骨损伤和破骨细胞活动减弱。此外，tau缺乏导致了滑膜中经典激活的1型(M1)巨噬细胞极化的抑制。Tau是一种在RA发病机制中尚未被认识的关键调节因子，可能为自身免疫性和炎症性关节疾病提供潜在的治疗靶点。
Tau protein serves a pro-inflammatory function in neuroinflammation. However, the role of tau in other inflammatory disorders such as rheumatoid arthritis (RA) is less explored. This study is to investigate the role of endogenous tau and the potential mechanisms in the pathogenesis of inflammatory arthritis. We established collagen-induced arthritis (CIA) model in wild-type and Tau-/- mice to compare the clinical score and arthritis incidence. Micro-CT analysis was used to evaluate bone erosion of ankle joints. Histological analysis was performed to assess inflammatory cell infiltration, cartilage damage, and osteoclast activity in the ankle joints. Serum levels of pro-inflammatory cytokines were measured by ELISA. The expression levels of macrophage markers were determined by immunohistochemistry staining and quantitative real-time PCR. Tau expression was upregulated in joints under inflammatory condition. Tau deletion in mice exhibited milder inflammation and protected against the progression of CIA, evidenced by reduced serum levels of pro-inflammatory cytokines and attenuated bone loss, inflammatory cell infiltration, cartilage damage, and osteoclast activity in the ankle joints. Furthermore, tau deficiency led to the inhibition of classically activated type 1 (M1) macrophage polarization in the synovium. Tau is a previously unrecognized critical regulator in the pathogenesis of RA and may provide a potential therapeutic target for autoimmune and inflammatory joint diseases.
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影响因子：
15.9
作者：
Fu, Wenyu;Hu, Wenhuo;Liu, Chuan-ju
通讯作者：
Liu, Chuan-ju
影响因子：
4.8
作者：
Fu, Wenyu;Hu, Wenhuo;Liu, Chuan-ju
通讯作者：
Liu, Chuan-ju
影响因子：
12.7
作者：
Guo T;Noble W;Hanger DP
通讯作者：
Hanger DP
影响因子：
168.9
作者：
Burmester, Gerd R.;Pope, Janet E.
通讯作者：
Pope, Janet E.
DOI：
10.1186/ar86
发表时间：
2000
期刊：
Arthritis research
影响因子：
--
作者：
Kinne RW;Bräuer R;Stuhlmüller B;Palombo-Kinne E;Burmester GR
通讯作者：
Burmester GR