Lam S H, Sin Y M, Gong Z, Lam T J
Department of Biological Sciences, National University of Singapore.
Gen Comp Endocrinol. 2005 Jul;142(3):325-35. doi: 10.1016/j.ygcen.2005.02.004. Epub 2005 Apr 7.
Effects of thyroxine (T4) and methimazole (MMI) on the development of the zebrafish immune system were investigated using continuous immersion treatment experiments. The effects of the treatments on thymus development were determined using computer-aided thymus morphometric analyses on in situ hybridization serial sections of the thymus while the effects on immune-related gene expression levels were monitored using quantitative real-time PCR. The findings indicate that thymus development and thymopoiesis, as indicated by thymus size, thymus Rag-1-positive region, and TCRAC expression level, were affected by T4 and MMI-treatments. With the exception of Ikaros, MMI-treated fish has lower immune-related gene expression levels, although it is not certain whether the effect resulted indirectly from the concomitant growth-retardation and/or directly from an effect on lymphopoiesis itself. The findings were comparable with those in mammalian system, thus providing the first evidence that the thyroid relationship with thymus development and lymphopoiesis is likely to be conserved from fish to higher vertebrates. It suggests the possibility of using zebrafish as a model system to investigate the molecular mechanisms involved in thyroid hormone-dependent disorders in the immune system.
通过连续浸泡处理实验，研究了甲状腺素（T4）和甲巯咪唑（MMI）对斑马鱼免疫系统发育的影响。利用计算机辅助的胸腺形态计量学分析方法，对胸腺原位杂交系列切片进行分析，以确定处理对胸腺发育的影响，同时使用定量实时PCR监测处理对免疫相关基因表达水平的影响。研究结果表明，胸腺大小、胸腺Rag-1阳性区域和TCRAC表达水平所表明的胸腺发育和胸腺细胞生成受到T4和MMI处理的影响。除Ikaros外，MMI处理的鱼免疫相关基因表达水平较低，尽管尚不确定这种影响是间接由伴随的生长迟缓导致的，还是直接由对淋巴细胞生成本身的影响导致的。这些发现与哺乳动物系统中的发现相当，从而首次证明甲状腺与胸腺发育和淋巴细胞生成之间的关系可能从鱼类到高等脊椎动物都是保守的。这表明有可能将斑马鱼用作模型系统，以研究免疫系统中甲状腺激素依赖性疾病所涉及的分子机制。
