The Role of IL-17 and TH17 Cells in the Bone Catabolic Activity of PTH.
The Role of IL-17 and TH17 Cells in the Bone Catabolic Activity of PTH.
复制标题
DOI：
10.3389/fimmu.2016.00057
复制
发表时间：
2016
影响因子：
7.3
通讯作者：
Pacifici R
中科院分区：
文献类型：
--
作者：
Pacifici R
骨免疫学是致力于研究免疫系统和骨之间相互作用的研究领域。在健康和疾病中调节骨骼的免疫系统细胞中有T淋巴细胞，T细胞分泌炎性/破骨细胞生成细胞因子如RANKL、TNF和IL-17，以及刺激骨形成的因子，包括Wnt配体。此外，T细胞通过其表面表达的CD 40 L和其他共刺激分子调节基质细胞的分化和寿命。共识是甲状旁腺激素（PTH）通过增加骨细胞和成骨细胞产生RANKL来诱导骨丢失。然而，新的证据表明，PTH扩增了Th 17细胞，并增加了小鼠和人类的IL-17水平。在小鼠中的研究进一步表明，Th 17细胞产生的IL-17作为“上游细胞因子”，增加成骨细胞和骨细胞对PTH的敏感性。因此，PTH刺激RANKL的骨细胞和成骨细胞释放。因此，PTH仅在IL-17信号传导存在下引起骨丢失。本文综述了PTH的作用不仅是通过成骨细胞和骨细胞，而且还通过T细胞和IL-17介导的证据。
Osteoimmunology is field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate the skeleton in health and disease are T lymphocytes, T cells secrete inflammatory/osteoclastogenic cytokines such as RANKL, TNF, and IL-17, as well as factors that stimulate bone formation, including Wnt ligands. In addition, T cells regulate the differentiation and life span of stromal cells via CD40L and other costimulatory molecules expressed on their surface. Consensus exists that parathyroid hormone (PTH) induces bone loss by increasing the production of RANKL by osteocytes and osteoblast. However, new evidence suggests that PTH expands Th17 cells and increases IL-17 levels in mice and humans. Studies in the mouse of further shown that Th17 cell produced IL-17 acts as an “upstream cytokine” that increases the sensitivity of osteoblasts and osteocytes to PTH. As a result, PTH stimulates osteocytic and osteoblastic release of RANKL. Therefore, PTH cause bone loss only in the presence of IL-17 signaling. This article reviews the evidence that the effects of PTH are mediated not only by osteoblasts and osteocytes, but also T cells and IL-17.