Kuo Jui-Fang, Wu Hsin-Ying, Tung Chun-Wei, Huang Wei-Hsiang, Lin Chen-Si, Wang Chia-Chi
School of Veterinary Medicine, National Taiwan University, Taipei 106, Taiwan.
Laboratory Animal Center, National Health Research Institutes, Miaoli County 350, Taiwan.
Chem Res Toxicol. 2024 Sep 16;37(9):1488-1500. doi: 10.1021/acs.chemrestox.4c00060. Epub 2024 Aug 14.
The susceptibility of the immune system to immunotoxic chemicals is evident, particularly in the thymus, a vital primary immune organ prone to atrophy due to exposure to toxicants. Fipronil (FPN), a widely used insecticide, is of concern due to its potential neurotoxicity, hepatotoxicity, and immunotoxicity. Our previous study showed that FPN disturbed the antigen-specific T-cell functionality . As T-cell lineage commitment and thymopoiesis are closely interconnected with the normal function of the T-cell-mediated immune responses, this study aims to further examine the toxic effects of FPN on thymocyte development. In this study, 4-week-old BALB/c mice received seven doses of FPN (1, 5, 10 mg/kg) by gavage. Thymus size, medulla/cortex ratio, total thymocyte counts, double-positive thymocyte population, and IL-7-positive cells decreased dose-dependently. IL-7 aids the differentiation of early T-cell precursors into mature T cells, and several essential genes contribute to the maturation of T cells in the thymus. 1 ensures that the thymic microenvironment is suitable for the maturation of T-cell precursors. 1 is involved in specifying lymphoid cells and maintaining T-cell development in the thymus. The collaboration fosters a supportive thymic milieu to promote the formation of functional T cells. The expression of 7, 7, , , 1, and 1 genes in the thymus was significantly diminished in FPN-treated groups with the concordance with the reduction of IL-7 signaling proteins (IL-7, IL-7R, c-KIT, SCF, LYL1, FOXO3A, and GABPA), suggesting that the dysregulation of T-cell lineage-related genes may contribute to the thymic atrophy induced by FPN. In addition, FPN disturbed the functionality of thymocytes with an increase of IL-4 and IFN-γ production and a decrease of IL-2 secretion after T-cell mitogen stimulation . Collectively, FPN significantly deregulated genes related to T-cell progenitor differentiation, survival, and expansion, potentially leading to impaired thymopoiesis.
免疫系统对免疫毒性化学物质的易感性是明显的，特别是在胸腺中，胸腺是一个重要的初级免疫器官，由于接触毒物而容易发生萎缩。氟虫腈（FPN）是一种广泛使用的杀虫剂，因其潜在的神经毒性、肝毒性和免疫毒性而受到关注。我们之前的研究表明，FPN扰乱了抗原特异性T细胞的功能。由于T细胞谱系定向和胸腺生成与T细胞介导的免疫反应的正常功能密切相关，本研究旨在进一步研究FPN对胸腺细胞发育的毒性作用。在本研究中，4周龄的BALB/c小鼠经口灌胃接受七剂FPN（1、5、10mg/kg）。胸腺大小、髓质/皮质比、胸腺细胞总数、双阳性胸腺细胞群体和IL-7阳性细胞呈剂量依赖性下降。IL-7有助于早期T细胞前体分化为成熟T细胞，并且几个关键基因有助于胸腺中T细胞的成熟。1确保胸腺微环境适合T细胞前体的成熟。1参与确定淋巴细胞并维持胸腺中T细胞的发育。这种协作促进了支持性的胸腺环境，以促进功能性T细胞的形成。在FPN处理组中，胸腺中7、7、、、1和1基因的表达显著降低，这与IL-7信号蛋白（IL-7、IL-7R、c-KIT、SCF、LYL1、FOXO3A和GABPA）的减少一致，表明T细胞谱系相关基因的失调可能导致FPN诱导的胸腺萎缩。此外，FPN扰乱了胸腺细胞的功能，T细胞有丝分裂原刺激后IL-4和IFN-γ产生增加，IL-2分泌减少。总体而言，FPN显著失调了与T细胞祖细胞分化、存活和扩增相关的基因，可能导致胸腺生成受损。
