胸腺再生的研究进展与策略

Progresses in therapeutic strategies for thymic rejuvenation

胸腺是人类重要的中枢免疫器官,是T细胞分化、发育、成熟的场所。然而,随着年龄的增长,胸腺出现增龄性萎缩和功能衰退,主要表现为腺体变小,细胞结构破坏和初始T淋巴细胞的输出减少,从而导致机体免疫力下降,罹患感染、自身免疫性疾病和肿瘤的风险增加。此外,骨髓移植、放化疗以及病毒感染导致的胸腺损伤也能引起机体免疫系统功能的降低。近年来,胸腺萎缩的发生机制和促进胸腺再生的方法已经成为免疫学领域的热点研究问题。本文将以胸腺基质微环境及其与胸腺细胞间相互作用为关键点,就性激素、细胞因子、生长因子、生长激素、转录因子、细胞移植和micro RNA等在促进胸腺再生方面的研究进展进行综述,并简要讨论现存的问题和未来的研究方向。

The thymus is a vital primary lymphoid organ that provides unique microenvironments for the proliferation,differentiation,and maturation of T cells. With advancing age,however,the thymus gradually undergoes age-related involution and reduction in immune function,which are characterized by decreases in tissue size,cellularity,and na？ve T cell output. This dynamic process leads to the reduced efficacy of the immune system with age and contributes to the increased susceptibility to infection,autoimmune disease,and cancer. In addition,bone marrow transplantation,radio-chemotherapy and virus infection also impair the thymus and give rise to the decline in immune function. Therefore,understanding the molecular mechanisms involved in age-related thymic involution and development of novel therapeutic strategies for thymic rejuvenation have gained considerable interests in recent years. This review emphasizes thymic microenvironments and thymocyte-stromal cell interactions and summarizes our current knowledge about thymic rejuvenation in terms of sex steroid,cytokines,growth factors,hormones,transcription factors,cell graft,and micro RNAs. At the end of each discussion,we also highlight unanswered issues and describe possible future research directions.