Thymus: the next (re)generation.
Thymus: the next (re)generation.
复制标题
DOI：
10.1111/imr.12418
复制
发表时间：
2016-05
影响因子：
8.7
通讯作者：
van den Brink MR
中科院分区：
文献类型：
--
作者：
Chaudhry MS;Velardi E;Dudakov JA;van den Brink MR
作为T细胞发育的主要部位，胸腺在产生强大而自我耐受的适应性免疫反应中起着关键作用，在面对病原体或肿瘤的潜在威胁时至关重要。随着胸腺作用的重要性增加，人们也认识到胸腺对急性和慢性损伤都非常敏感。在一系列有毒侮辱之后，胸腺经历了快速的退化，作为老化过程的一部分，胸腺也会退化，尽管速度比许多其他组织更快。然而，胸腺能够再生，在一定程度上恢复其功能。这种内源性胸腺再生的潜在机制包括角质细胞生长因子(KGF)信号转导，以及最近被描述的先天淋巴样细胞产生白介素22(IL-22)的途径，以响应双阳性胸腺细胞的丧失和树突状细胞上调IL-23。内源性修复无法完全恢复胸腺，特别是在老年人群中，这为需要外源性策略帮助再生甚至取代胸腺功能铺平了道路。目前正在临床试验的治疗方法包括KGF，使用细胞因子IL-7和IL-22，以及激素调节，包括生长激素注射和性类固醇抑制。在临床前环境中出现了更多的新策略，包括使用前体T细胞和胸腺生物工程。这些策略的使用带来了希望，对许多患者来说，胸腺的下一次再生更近了一步。
As the primary site of T cell development, the thymus plays a key role in the generation of a strong yet self-tolerant adaptive immune response, essential in the face of the potential threat from pathogens or neoplasia. As the importance of the role of the thymus has grown, so too has the understanding that it is extremely sensitive to both acute and chronic injury. The thymus undergoes rapid degeneration following a range of toxic insults, and also involutes as part of the aging process, albeit at a faster rate than many other tissues. The thymus is, however, capable of regenerating, restoring its function to a degree. Potential mechanisms for this endogenous thymic regeneration include keratinocyte growth factor (KGF) signaling, and a more recently described pathway in which innate lymphoid cells produce interleukin-22 (IL-22) in response to loss of double positive thymocytes and upregulation of IL-23 by dendritic cells. Endogenous repair is unable to fully restore the thymus, particularly in the aged population, and this paves the way towards the need for exogenous strategies to help regenerate or even replace thymic function. Therapies currently in clinical trials include KGF, use of the cytokines IL-7 and IL-22, and hormonal modulation including growth hormone administration and sex steroid inhibition. Further novel strategies are emerging in the pre-clinical setting, including the use of precursor T cells and thymus bioengineering. The use of such strategies offers hope that for many patients, the next regeneration of their thymus is a step closer.