The members of the Tumor Necrosis Factor (TNF) superfamily, the ligand lymphotoxin α1β2 (LTα1β2) and its unique receptor lymphotoxin β receptor (LTβR), play a pivotal role in the establishment and regulation of the immune system by allowing a tight communication between lymphocytes and stromal cells. Recent advances using transgenic mice harboring a specific deletion of the Ltbr gene in distinct stromal cells have revealed important roles for LTβR signaling in the thymic function that ensures the generation of a diverse and self-tolerant T-cell repertoire. In this review, we summarize our current knowledge on this signaling axis in the thymic homing of lymphoid progenitors and peripheral antigen-presenting cells, the trafficking and egress of thymocytes, the differentiation of medullary thymic epithelial cells, and the establishment of central tolerance. We also highlight the importance of LTα1β2/LTβR axis in controlling the recovery of the thymic function after myeloablative conditioning regimen, opening novel perspectives in regenerative medicine.

肿瘤坏死因子 (TNF) 超家族的成员，配体淋巴毒素 α1β2 (LTα1β2) 及其独特的受体淋巴毒素 β 受体 (LTβR)，通过允许淋巴细胞之间的紧密联系，在免疫系统的建立和调节中发挥关键作用和基质细胞。使用携带Ltbr特定缺失的转基因小鼠的最新进展不同基质细胞中的基因揭示了 LTβR 信号在胸腺功能中的重要作用，可确保产生多样化和自我耐受的 T 细胞库。在这篇综述中，我们总结了我们目前对淋巴祖细胞和外周抗原呈递细胞的胸腺归巢、胸腺细胞的运输和出口、髓质胸腺上皮细胞的分化以及中枢耐受性的建立中的信号轴的了解。我们还强调了 LTα1β2/LTβR 轴在控制清髓性预处理方案后胸腺功能恢复中的重要性，为再生医学开辟了新的视角。