胸腺,T淋巴细胞发育和成熟的地方,对组织缺血或损伤等损伤敏感。这些损伤会导致胸腺萎缩并损害T细胞发育,可能损害适应性免疫。这项研究的目的是研究心肌梗塞(MI)是否会引起胸腺损伤以损害T淋巴细胞生成并揭示其潜在机制。与假对照相比,MI小鼠在MI后第7天表现出更小的胸腺,较低的细胞密度,以及不同发育阶段的胸腺细胞较少,提示MI后T淋巴细胞生成受损。因此,MI小鼠的脾脏有较少的T细胞和最近的胸腺移民(RTE),这意味着MI小鼠的胸腺比假手术对照组释放更少的成熟胸腺细胞。有趣的是,脾T细胞的分泌功能不受MI的影响。进一步的实验表明,MI小鼠胸腺细胞的减少是由于胸腺细胞凋亡增加。肾上腺切除术(ADX)可以预防MI引起的胸腺损伤和功能障碍,而在ADX+MI小鼠中补充皮质酮会重新诱导胸腺损伤和功能障碍,表明糖皮质激素介导由MI引发的胸腺损伤。嗜酸性粒细胞在照射后胸腺再生中起着至关重要的作用,嗜酸性粒细胞缺乏的小鼠在亚致死照射后表现出胸腺恢复受损。有趣的是,在MI后第14天,在野生型和嗜酸性粒细胞缺陷型小鼠中胸腺都完全再生,表明嗜酸性粒细胞对MI后胸腺再生并不重要。总之,我们的研究表明,MI诱导的糖皮质激素触发胸腺细胞凋亡和损害T淋巴细胞生成,导致成熟胸腺细胞释放到脾脏。
The thymus, where T lymphocytes develop and mature, is sensitive to insults such as tissue ischemia or injury. The insults can cause thymic atrophy and compromise T-cell development, potentially impairing adaptive immunity. The objective of this study was to investigate whether myocardial infarction (MI) induces thymic injury to impair T
lymphopoiesis and to uncover the underlying mechanisms. When compared with sham controls, MI mice at day 7 post-MI exhibited smaller thymus, lower cellularity, as well as less thymocytes at different developmental stages, indicative of T-
lymphopoiesis impairment following MI. Accordingly, the spleen of MI mice has less T cells and recent thymic emigrants (RTEs), implying that the thymus of MI mice releases fewer mature thymocytes than sham controls. Interestingly, the secretory function of splenic T cells was not affected by MI. Further experiments showed that the reduction of thymocytes in MI mice was due to increased thymocyte apoptosis. Removal of adrenal glands by adrenalectomy (ADX) prevented MI-induced thymic injury and dysfunction, whereas corticosterone supplementation in ADX + MI mice reinduced thymic injury and dysfunction, indicating that glucocorticoids mediate thymic damage triggered by MI. Eosinophils play essential roles in thymic regeneration postirradiation, and eosinophil-deficient mice exhibit impaired thymic recovery after sublethal irradiation. Interestingly, the thymus was fully regenerated in both wild-type and eosinophil-deficient mice at day 14 post-MI, suggesting that eosinophils are not critical for thymus regeneration post-MI. In conclusion, our study demonstrates that MI-induced glucocorticoids trigger thymocyte apoptosis and impair T
lymphopoiesis, resulting in less mature thymocyte release to the spleen.NEW & NOTEWORTHY The thymus is essential for maintaining whole body T-cell output. Thymic injury can adversely affect T
lymphopoiesis and T-cell immune response. This study demonstrates that MI induces thymocyte apoptosis and compromises T
lymphopoiesis, resulting in fewer releases of mature thymocytes to the spleen. This process is mediated by glucocorticoids secreted by adrenal glands. Therefore, targeting glucocorticoids represents a novel approach to attenuate post-MI thymic injury.