探索安全有效的免疫抑制方案一直是移植领域关注和研究的主要目标。肠道微生物具有免疫调节作用，并可抑制移植排斥反应，但相关机制尚不明确。我们前期研究发现：在小鼠皮肤移植急排模型中，将特定微生物植入受体肠道，仅需联合低剂量免疫抑制剂，即可抑制排斥反应，延长移植物存活。在小鼠肾移植急排模型中，仅将特定微生物植入受体肠道，亦可显著抑制排斥反应，同时发现肠粘膜ILCreg迁移进入移植肾，使移植肾Aire+ILC3数量增加，提示其可能是肠道微生物抑制排斥反应的关键。基于上述结果，我们提出“肠道微生物诱导肠粘膜ILCreg迁移至移植肾，使ILC3s转化为Aire+ILC3，通过抗原呈递作用减少T细胞活化，从而延长移植肾存活时间”的科学假说。本项目拟建立小鼠肾移植急排模型，探索ILCreg及Aire+ILC3在肠道微生物抑制排斥反应的作用，为肠道微生物今后在临床防治排斥反应及减少免疫抑制剂应用提供理论依据。

A significant topic of organ transplantation is to explore a immunosuppression with more safe and effective. Gut microbiota plays a pivotal role in the immune regulation, which has been confirmed to alleviate the allograft rejection. The gut microbiota has potential clinical prospects; however, the mechanism of its immunosuppression is still unknown. In a murine skin transplantation model of acute rejection, our previous study has demonstrated that a transfer of specific gut bacteria into the recipient with a low dose of immunosuppressant was able to alleviate the rejection and prolong the grafts survival time. Then, in a murine kidney transplantation model of acute rejection, only a transfer of specific gut bacteria can also significantly alleviate the rejection and prolong the grafts survival time. Meanwhile, the regulatory innate lymphocytes (ILCreg) migrated into the graft kidney which increased the number of Aire+ ILC3, suggesting that the Aire+ ILC3 may be a key point for the gut microbiota to inhibit rejection. Therefore, we propose that the specific gut microbiota promotes the migration of intestinal mucosal ILCreg to the graft kidney, inducing ILC3s into Aire+ ILC3. These cells further alleviate the acute rejection and prolong the graft kidney survival time by inhibiting the activation of T cells though antigen presentation. We will assess the hypothesis in a murine kidney transplantation model of acute rejection, revealing the effect of Aire+ ILC3 in gut microbiota-mediated immunosuppression. This topic will be of great significance to elucidate the mechanism of transplant rejection alleviation by the gut microbiota and provide a theoretical basis for gut microbiota related therapy clinically, which may prevent transplant rejection and reduce the dose of immunosuppressive agents.