Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Immunol Cell Biol. 2013 Jul;91(6):416-26. doi: 10.1038/icb.2013.22. Epub 2013 May 21.
Tyro3, Axl and Mer (TAM) receptor tyrosine kinases triple knockout (TAM(-/-)) mice are male infertile due to impaired spermatogenesis. However, the mechanism by which TAM receptors regulate spermatogenesis remains unclear. In this study, we demonstrate that the testicular immune homeostasis was impaired in TAM(-/-) mice. As development after the onset of sexual maturity, germ cells were progressively degenerated. Macrophages and lymphocytes infiltrated into the testis as TAM(-/-) mice aged. Moreover, the integrity of blood-testis barrier was impaired, and the autoantibodies against germ cell antigens were produced. Major inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein 1 were upregulated in the testis of TAM(-/-) mice, and predominantly located in Sertoli cells (SCs). In vitro assays showed that TAM(-/-) SCs secrete significantly high levels of inflammatory cytokines compared with wild-type SCs after coculture with apoptotic germ cells. These results suggest that TAM receptors are important in the maintenance of the immune homeostasis in the testis.
TAM 受体酪氨酸激酶三重敲除（TAM(-/-)) 小鼠由于精子发生受损而导致雄性不育。然而，TAM 受体调节精子发生的机制尚不清楚。在这项研究中，我们证明了 TAM(-/-) 小鼠的睾丸免疫稳态受损。随着性成熟后发育，精原细胞逐渐退化。随着 TAM(-/-) 小鼠年龄的增长，巨噬细胞和淋巴细胞浸润到睾丸中。此外，血睾屏障的完整性受损，产生了针对生殖细胞抗原的自身抗体。主要的炎症细胞因子，包括肿瘤坏死因子-α、白细胞介素-6 和单核细胞趋化蛋白 1，在 TAM(-/-) 小鼠的睾丸中上调，主要位于支持细胞（SCs）中。体外实验表明，与野生型 SC 相比，TAM(-/-)SC 在与凋亡的生殖细胞共培养后分泌的炎症细胞因子水平显著升高。这些结果表明，TAM 受体在睾丸免疫稳态的维持中具有重要作用。
