Abstract:
The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 μg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.
摘要:
Hedgehog(Hh)信号通路参与T细胞的分化和发育,在T细胞发育的不同阶段起着重要的调节作用。我们先前的研究表明,产前暴露于葡萄球菌肠毒素B(SEB)会改变后代胸腺中T细胞亚群的百分比。然而,目前尚不清楚产前SEB暴露是否会影响胸腺T细胞中的Hh信号通路.在本研究中,妊娠第16天的怀孕大鼠静脉注射15μgSEB一次,对新生和成年后代大鼠的胸腺进行无菌采集,以研究SEB对Hh信号通路的影响。首先发现产前SEB暴露明显导致新生和成年子代大鼠胸腺组织中Hh信号通路Shh和Dhh配体表达增加,但显著降低了膜受体Ptch1和Smo的表达水平,转录因子Gli1,以及CyclinD1,C-myc,和N-myc在胸腺T细胞Hh信号通路中的作用。这些数据表明,产前SEB暴露抑制了新生儿后代胸腺T淋巴细胞中的Hh信号通路,这种效应可以通过印记效应在成年后代中保持。