胸腺损伤是感染、放疗、化疗等过程中常见的病理现象之一。损伤后的胸腺重建对于T细胞数量和功能的恢复，以及对相关疾病的治疗都具有十分重要的意义。胸腺重建过程中的细胞对话和分子调控机制尚不清楚。我们前期工作表明，基质细胞表达的淋巴毒素beta受体（LTbR）对于伽玛射线照射引起的胸腺损伤后的重建至关重要，揭示了LTbR在胸腺生物学中的一个全新的功能。本研究将围绕表达在胸腺基质细胞上的LTbR及其主要表达在胸腺细胞和LTi细胞的配体LT和LIGHT，研究两者的相互作用如何影响了胸腺上皮细胞，血管内皮细胞的数量或功能，如何影响了胸腺细胞从ETP（或更早期祖细胞阶段）到DP阶段的迁移、分化和扩增。本项目有望揭示一条关于胸腺重建的全新的细胞对话和分子调控机制，并为胸腺重建靶向的免疫治疗提供新的理论依据。

Thymic injury is a very common pathological phenomenon during infection, radiation therapy and chemotherapy. Proper thymic regeneration is critical for the reconstitution of T cell immune compartment. While the molecular and cellular mechanisms of thymus development has been extensively investigated and well understood, it is remains largely unclear how the thymic regeneration is regulated at both cellular and molecular levels, which hinders the development of T cell reconstitution therapy. Our preliminary study has surprisingly found a novel role of LTbR in thymic regeneration after sub-lethal total body gamma irradiation. Further work suggested that LTbR controls early thymocytes development through radioresistant cells, likely stromal cells. In current research, we will determine, at both molecular and cellular levels, how LTbR controls thymic stromal cells for thymic regeneration. Thus, our study will likely reveal a novel crosstalk pathway and mechanisms underlying thymic regeneration.