兰克尔
FOXP3型
免疫学
关节炎
促炎细胞因子
破骨细胞
炎症
过继性细胞移植
医学
骨吸收
骨免疫学
骨质疏松症
类风湿性关节炎
白细胞介素17
内科学
骨重建
骨髓
骨矿物
免疫系统
T细胞
受体
激活剂(遗传学)
作者
Anaïs Levescot,Margaret H. Chang,Julia Schnell,Nathan Nelson-Maney,Jing Yan,Marta Martínez-Bonet,Ricardo Grieshaber-Bouyer,Pui Y. Lee,Kevin Wei,Rachel B Blaustein,Allyn Morris,Alexandra Wactor,Yoichiro Iwakura,James A. Lederer,Deepak A. Rao,Julia F. Charles,Peter A. Nigrovic
摘要
IL-1β is a proinflammatory mediator with roles in innate and adaptive immunity. Here we show that IL-1β contributes to autoimmune arthritis by inducing osteoclastogenic capacity in Tregs. Using mice with joint inflammation arising through deficiency of the IL-1 receptor antagonist (Il1rn-/-), we observed that IL-1β blockade attenuated disease more effectively in early arthritis than in established arthritis, especially with respect to bone erosion. Protection was accompanied by a reduction in synovial CD4+Foxp3+ Tregs that displayed preserved suppressive capacity and aerobic metabolism but aberrant expression of RANKL and a striking capacity to drive RANKL-dependent osteoclast differentiation. Both Il1rn-/- Tregs and wild-type Tregs differentiated with IL-1β accelerated bone erosion upon adoptive transfer. Human Tregs exhibited analogous differentiation, and corresponding RANKLhiFoxp3+ T cells could be identified in rheumatoid arthritis synovial tissue. Together, these findings identify IL-1β-induced osteoclastogenic Tregs as a contributor to bone erosion in arthritis.
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