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. 2019 Jun 25;10:1409. doi: 10.3389/fimmu.2019.01409

Figure 3.

Figure 3

The role of S1P-S1PR1 signaling in osteoimmunology. S1P-S1PR1 signaling is greatly involved in the interaction between immune system and bone remodeling. On one hand, S1PR1 directly affects osteoclastogenesis by inducing the migration of osteoclast-precursors. The direct effect of S1P on osteoclast-precursors results in reduced osteoclastogenesis; however, it induces RANKL production of osteoblasts and facilitating the RANKL-RANK mediated osteoclastogenesis. S1P also induces the migration of MSCs and osteogenesis by activating S1PR1. On the other hand, S1P-S1PR1 signaling participates in immune regulation, which affects the polarization and function of T-helper cells. S1P-S1PR1 signaling induces the differentiation and function of Th17 cells (known as inducing osteoclastogenesis) while impedes that of Treg cells (known as reducing osteoclastogenesis); therefore facilitating osteoclastogenesis. S1P also induces the function of Th2 cells while reduces that of Th1 cells, which affects the macrophage phenotype; also, S1P directly induces the transition of M1 to M2 phenotype by activating S1PR1. This conversion of pro-inflammatory M1 macrophages to tissue-engineering M2 macrophages therefore impedes osteoclastogenesis, which might also affect osteogenesis. S1P, sphingosine-1-phosphate; S1PR, sphingosine-1-phosphate receptor(s); S1PR1, sphingosine-1-phosphate receptor 1; MSC, mesenchymal stem cell; Th1/2/17, type 1/2/17 helper T cell; M1/M2, M1/M2 macrophage; Treg, regulatory T cell; IFNγ, interferon-γ; IL-4/10/17, interleukin-4/10/17.