Institute of Reproductive Health, Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, China.
Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, China.
Front Immunol. 2021 Oct 26;12:743354. doi: 10.3389/fimmu.2021.743354. eCollection 2021.
Macrophages are functionally plastic and can thus play different roles in various microenvironments. Testis is an immune privileged organ, and testicular macrophages (TMs) show special immunosuppressive phenotype and low response to various inflammatory stimuli. However, the underlying mechanism to maintain the immunosuppressive function of TMs remains unclear. S100A9, a small molecular Ca binding protein, is associated with the immunosuppressive function of macrophages. However, no related research is available about S100A9 in mouse testis. In the present study, we explored the role of S100A9 in TMs. We found that S100A9 was expressed in TMs from postnatal to adulthood and contributed to maintaining the immunosuppressive phenotype of TMs, which is associated with the activation of PI3K/Akt pathway. S100A9 treatment promotes the polarization of bone marrow-derived macrophages from M0 to M2 . S100A9 was significantly increased in TMs following UPEC-infection and elevated S100A9 contributed to maintain the M2 polarization of TMs. Treatment with S100A9 and PI3K inhibitor decreased the proportion of M2-type TMs in control and UPEC-infected mouse. Our findings reveal a crucial role of S100A9 in maintaining the immunosuppressive function of TMs through the activation of PI3K/Akt pathway, and provide a reference for further understanding the mechanism of immunosuppressive function of TMs.
巨噬细胞具有功能可塑性，因此可以在不同的微环境中发挥不同的作用。睾丸是一个免疫特惠器官，睾丸巨噬细胞（TMs）表现出特殊的免疫抑制表型，对各种炎症刺激的反应较低。然而，维持 TMs 免疫抑制功能的潜在机制尚不清楚。S100A9 是一种小分子 Ca 结合蛋白，与巨噬细胞的免疫抑制功能有关。然而，目前还没有关于 S100A9 在小鼠睾丸中的相关研究。在本研究中，我们探讨了 S100A9 在 TMs 中的作用。我们发现 S100A9 在出生后至成年期的 TMs 中表达，并有助于维持 TMs 的免疫抑制表型，这与 PI3K/Akt 通路的激活有关。S100A9 处理可促进骨髓来源的巨噬细胞从 M0 向 M2 极化。UPEC 感染后 TMs 中 S100A9 明显增加，升高的 S100A9 有助于维持 TMs 的 M2 极化。用 S100A9 和 PI3K 抑制剂处理可降低对照组和 UPEC 感染小鼠中 M2 型 TMs 的比例。我们的研究结果揭示了 S100A9 通过激活 PI3K/Akt 通路在维持 TMs 免疫抑制功能中的关键作用，并为进一步了解 TMs 免疫抑制功能的机制提供了参考。
