TSLP is a negative regulator of RANKL-induced osteoclastogenesis.
TSLP is a negative regulator of RANKL-induced osteoclastogenesis.
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TSLP 是 RANKL 诱导的破骨细胞生成的负调节因子。
DOI：
10.1016/j.bbrc.2020.05.055
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Ohno;T.;Nakamura;T.;Nakae;S.;Morita;H.;Matsumoto;K.;Takeda;K.;Okumura;K.;and Azuma;T.
胸腺基质淋巴细胞生成素（TSLP）是IL-2细胞因子家族的成员，已知其激活2型先天性淋巴细胞、肥大细胞和Th2细胞;这种激活导致过敏性炎症和宿主对寄生虫的防御。TSLP也被证明可以促进Th17介导的免疫应答，例如在类风湿性关节炎的发展中观察到的免疫应答;然而，其在破骨细胞生成中的作用仍然知之甚少。在这里，我们研究了TSLP在RANKL诱导的小鼠骨髓源性巨噬细胞（BMSCs）破骨细胞分化中的功能参与。RANK −和RANK+巨噬细胞均表达TSLP受体（TSLPR），而RANK+破骨细胞前体在RANKL刺激后保持TSLPR表达。TSLP刺激导致RANK诱导的破骨细胞分化在野生型Bcl3中受到抑制，但Tslpr −/− Bcl3没有; TSLP刺激还导致破骨细胞基因表达（Nfatc1、Acp5、Mmp9和Ctsk）受到抑制。TSLP的这些抑制作用在STAT1抑制后显著降低。最后，我们发现LPS刺激诱导小鼠颅骨成骨细胞产生TSLP，而不是BLP。总之，这些观察结果表明TSLP直接作用于破骨细胞前体以抑制破骨细胞生成。因此，成骨细胞，沿着其他TSLP产生细胞，可能有助于抑制炎症条件下的破骨细胞生成。
Thymic stromal lymphopoietin (TSLP) is a member of the IL-2 cytokine family, which is known to activate type 2 innate lymphoid cells, mast cells, and Th2 cells; this activation results in allergic inflammation and host defense against parasites. TSLP has also been shown to promote Th17-mediated immune responses, such as those observed in the development of rheumatoid arthritis; however, its role in osteoclastogenesis remains poorly understood. Here, we investigated the functional involvement of TSLP in RANKL-induced osteoclast differentiation from murine bone marrow-derived macrophages (BMMs). Both RANK−and RANK+macrophages expressed TSLP receptor (TSLPR), while RANK+osteoclast precursors maintained TSLPR expression after RANKL stimulation. TSLP stimulation led to inhibition of RANK-induced osteoclast differentiation in wild-type BMMs, but notTslpr−/−BMMs; TSLP stimulation also led to suppression of osteoclastogenic gene expression (Nfatc1,Acp5,Mmp9, andCtsk). These inhibitory effects of TSLP were significantly reduced following STAT1 inhibition. Finally, we found that LPS stimulation induced TSLP production in murine calvarial osteoblasts, but not BMMs. Together, these observations suggest that TSLP acts directly on osteoclast precursors to suppress osteoclastogenesis. Osteoblasts, along with other TSLP-producing cells, may therefore contribute to the inhibition of osteoclastogenesis under inflammatory conditions.