Department of Molecular and Human Genetics, Institute of Science, Banaras Hindu University, Varanasi, India.
Genes Cells. 2021 Apr;26(4):254-263. doi: 10.1111/gtc.12837. Epub 2021 Mar 18.
Toll pathway is the center for the function of immune system in both Drosophila and mammals. Toll pathway in Drosophila gets activated upon binding of the ligand Spätzle to the receptor, Toll, triggering a series of proteolytic cascade culminating into the activation of the NF-κB factors Dorsal and/or Dif (Dorsal-related immunity factor). Inappropriate activation of the Toll pathway is often associated with systemic inflammation phenotype in the absence of infection, and thus, it is important to understand the regulation of Toll signaling. Deltex (Dx) is a context-dependent regulator of Notch signaling and has been linked with cell-mediated immunity in the mammalian system lately. However, the unambiguous role of Dx in humoral and cell-mediated immunity is yet to be explored. Our study unravels the novel role of Dx in Toll pathway activation. Gain of function of dx in Drosophila larvae results in increased melanotic mass formation and increased lamellocyte production. Our results also reveal the nuclear accumulation of transcription factors Dorsal and Dif and expression of Toll-associated antimicrobial peptides (AMP) in Dx over-expression background. Further, we also tried to elucidate the role of Dx in JNK-independent Toll activation. Here we present Dx as a novel candidate in the regulation of Toll pathway.
Toll 途径是果蝇和哺乳动物免疫系统功能的核心。果蝇中的 Toll 途径在配体 Spätzle 与受体 Toll 结合后被激活，触发一系列蛋白水解级联反应，最终导致 NF-κB 因子 Dorsal 和/或 Dif（Dorsal 相关免疫因子）的激活。Toll 途径的异常激活常与感染缺失时的全身炎症表型有关，因此，了解 Toll 信号的调节非常重要。Deltex (Dx) 是 Notch 信号的上下文依赖性调节剂，最近与哺乳动物系统中的细胞介导免疫有关。然而，Dx 在体液和细胞介导免疫中的明确作用尚未得到探索。我们的研究揭示了 Dx 在 Toll 途径激活中的新作用。在果蝇幼虫中，dx 的功能获得导致黑色素团形成增加和 lamellocyte 产生增加。我们的结果还揭示了转录因子 Dorsal 和 Dif 的核积累以及 Toll 相关抗菌肽 (AMP) 在 Dx 过表达背景下的表达。此外，我们还试图阐明 Dx 在 JNK 非依赖性 Toll 激活中的作用。在这里，我们提出 Dx 是 Toll 途径调节的一个新候选分子。
