Unidade de Imunologia Clínica, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Curr Opin Organ Transplant. 2013 Jun;18(3):363-8. doi: 10.1097/MOT.0b013e3283615df9.
Maintenance of T-cell function and modulation of tolerance are critical issues in organ transplantation. The thymus is the primary organ for T-cell generation, and a preserved thymic function is essential for a self-tolerant diverse T-cell repertoire. Transplant procedures and related immunosuppressive drugs may hinder thymic integrity and function. We review here the recent advances in understanding the regulation of the unique thymic microenvironment with relevance for the field of transplantation.
Recent studies have assigned a role for IL-22 in the regeneration of thymic epithelium, and for microRNAs in the modulation of its survival and function. The interplay of key molecules in the cross-talk between thymic epithelial cells and thymocytes was depicted, opening new perspectives for the in-vitro recapitulation of T-cell development and for thymic transplantation. Additionally, the thymus was shown to be able to sustain thymocyte progenitor renewal.
These findings open new venues of research toward therapeutic interventions in the endogenous thymus to modulate or reconstitute the immune system; thymic transplantation; and the future development of artificial thymus, which would represent an important tool to achieve tolerance across the histocompatibility barriers.
在器官移植中,维持 T 细胞功能和调节免疫耐受是关键问题。胸腺是 T 细胞生成的主要器官,保留胸腺功能对于自身耐受的多样化 T 细胞库至关重要。移植程序和相关的免疫抑制药物可能会阻碍胸腺的完整性和功能。我们在这里回顾了近年来对与移植领域相关的独特胸腺微环境的调控的理解进展。
最近的研究将 IL-22 在胸腺上皮细胞的再生中的作用,以及 microRNAs 在其存活和功能的调节中的作用进行了分配。描绘了胸腺上皮细胞和胸腺细胞之间串扰的关键分子的相互作用,为 T 细胞发育和胸腺移植的体外再现开辟了新的视角。此外,还表明胸腺能够维持胸腺细胞祖细胞的更新。
这些发现为治疗性干预内源性胸腺以调节或重建免疫系统、胸腺移植以及人工胸腺的未来发展开辟了新的研究途径,这将代表实现组织相容性障碍耐受的重要工具。