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上皮组织作为生物体免疫系统的第一道屏障,经常会遭受各种导致结构破坏的生化或物理侵扰。但是我们对上皮细胞免疫如何感知这些危险信号并激发免疫应答还不十分清楚。本文我们利用秀丽线虫表皮细胞为模型来研究这一科学问题。线虫表皮在遭到穿透性真菌感染或者机械损伤后,会激发表皮固有免疫应答,引起下游抗菌肽nlp-29的表达释放。我们通过全基因组突变筛选的方法,鉴定得到了一个编码含EGF样结构域蛋白的保守基因,并命名为suei-5(suppressor of epidermal immune response 5)。荧光融合蛋白转基因报告虫株显示SUEI-5主要表达在线虫成虫阶段,并且在具有免疫防御功能的表皮上皮细胞中高表达。suei-5基因突变不但显著阻断了真菌感染或机械损伤诱发的表皮固有免疫应答和抗菌肽表达上调,而且也抑制了表皮细胞内部结构缺失引起的固有免疫应答。综上所述,我们的研究发现了一个新型的感知外界侵扰的免疫识别分子,揭示了一种进化上保守的上皮细胞识别危险以及激活免疫应答的分子机制。
Epithelial tissue, as the first barrier to the immune system of living organisms, often suffers from various biochemical or physical disturbances leading to structural breakdown. But it is unclear how we sense these dangerous signals and stimulate the immune response to epithelial cells. In this paper, we use the nematode epidermal cells as a model to study this scientific issue. Nematode epidermis in penetrating fungal infection or mechanical damage, it will stimulate the epidermal innate immune response, causing the downstream release of the expression of antibacterial peptide nlp-29. We identified a conserved gene encoding EGF-like domain-containing protein by a genome-wide mutation screening method and named suei-5 (suppressor of epidermal immune response 5). Fluorescent fusion protein transgenic reporter strains showed that SUEI-5 was mainly expressed in adult stage of nematodes and was highly expressed in epidermal epithelial cells with immune defense function. The suei-5 gene mutation not only significantly blocked the innate and epicardial immune responses induced by fungal infection or mechanical injury, but also inhibited the innate immune response caused by the structural loss of the epidermal cells. In summary, our study uncovered a new type of immune recognition molecule that is intrusive to the outside world, revealing a molecular mechanism that evolutionarily conserves the danger of epithelial cells recognizing and activating an immune response.