黑素瘤缺乏因子2(absent in melanoma2,AIM2)是一种主要定位于细胞质的蛋白质,其N端含有热蛋白(pyrin)结构域(PYD),而在C端为寡核苷酸/寡糖结合结构域。当AIM2与细胞质双链DNA结合后,它通过PYD相互作用而招募另一个细胞质蛋白质ASC,并...黑素瘤缺乏因子2(absent in melanoma2,AIM2)是一种主要定位于细胞质的蛋白质,其N端含有热蛋白(pyrin)结构域(PYD),而在C端为寡核苷酸/寡糖结合结构域。当AIM2与细胞质双链DNA结合后,它通过PYD相互作用而招募另一个细胞质蛋白质ASC,并诱导了炎性体的组装,从而引起随后胱天蛋白酶1(caspase-1)的激活和IL-1β的产生,诱导先天免疫反应甚至导致pyroptosis样细胞死亡。AIM2作为细胞质双链DNA感应蛋白的研究对先天免疫系统的理解和自身免疫性疾病(如系统性红斑狼疮等)的新治疗药物的设计具有重要意义。展开更多
Background: It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. Observations: We observ...Background: It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. Observations: We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16%of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin. Conclusions: This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.展开更多
文摘黑素瘤缺乏因子2(absent in melanoma2,AIM2)是一种主要定位于细胞质的蛋白质,其N端含有热蛋白(pyrin)结构域(PYD),而在C端为寡核苷酸/寡糖结合结构域。当AIM2与细胞质双链DNA结合后,它通过PYD相互作用而招募另一个细胞质蛋白质ASC,并诱导了炎性体的组装,从而引起随后胱天蛋白酶1(caspase-1)的激活和IL-1β的产生,诱导先天免疫反应甚至导致pyroptosis样细胞死亡。AIM2作为细胞质双链DNA感应蛋白的研究对先天免疫系统的理解和自身免疫性疾病(如系统性红斑狼疮等)的新治疗药物的设计具有重要意义。
文摘Background: It has been proposed that the innate immune system plays a central role in driving the autoimmune T-cell cascade leading to psoriasis; however, there is no direct evidence for this. Observations: We observed aggravation and spreading of a psoriatic plaque when treated topically with the toll-like receptor (TLR) 7 agonist imiquimod. The exacerbation of psoriasis was accompanied by a massive induction of lesional type I interferon activity, detected by MxA expression after imiquimod therapy. Since imiquimod induces large amounts of type I interferon production from TLR7-expressing plasmacytoid dendritic cell precursors (PDCs), the natural interferon-producing cells of the peripheral blood, we asked whether PDCs are present in psoriatic skin. We identified high numbers of PDCs in psoriatic skin lesions (up to 16%of the total dermal infiltrate) based on their coexpression of BDCA2 and CD123. By contrast, PDCs were present at very low levels in atopic dermatitis and not detected in normal human skin. Conclusions: This study shows that psoriasis can be driven by the innate immune system through TLR ligation. Furthermore, our finding that large numbers of PDCs infiltrate psoriatic skin suggests a role of lesional PDCs as type I interferon-producing targets for the TLR7 agonist imiquimod.
