The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients...
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The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation. We also found that an autophagy-based unconventional secretory pathway (autosecretion) dependent on ATG5 (autophagy related 5) and GORASP2 (golgi reassembly stacking protein 2) promoted psoriasiform KC inflammation. Moreover, the alarmin HMGB1 (high mobility group box 1) was more effective than other autosecretory proteins in regulating psoriasiform cutaneous inflammation. HMGB1 neutralization in autophagy-efficient KCs eliminated the differences in psoriasiform inflammation between Krt14(+/+)-Atg5(f/f) KCs and Krt14(Cre/+)-atg5(f/f) KCs, and conversely, recombinant HMGB1 almost completely restored psoriasiform inflammation in Krt14(Cre/+)-atg5(f/f) KCs in vivo. These results suggest that HMGB1-associated autosecretion plays a pivotal role in cutaneous inflammation. Finally, we demonstrated that Krt14(Cre/+)-hmgb1(f/f) mice displayed attenuated psoriatic inflammation due to the essential crosstalk between KC-specific HMGB1-associated autosecretion and gamma delta T cells. Thus, this study uncovered a novel autophagy mechanism in psoriasis pathogenesis, and the findings imply the clinical significance of investigating and treating psoriasis.
南大洋因其面积广阔等优势,能够存储更多的热量和二氧化碳(CO_(2)),因此在全球碳循环及气候变化中的地位十分重要。罗斯海作为南大洋第二大边缘海,是研究古海洋演化的理想海域。本研究采用罗斯海陆坡和海盆区的3根插管沉积物岩芯——BC008(水深1063 m,长27 cm,年龄6.0~14.8 ka B.P.)、BC010(水深2055 m,长44 cm,年龄0~15.5 ka B.P.)和BC006(水深2120 m,长54 cm,年龄0~22.3 ka B.P.),通过分析其生物硅含量及浮游有孔虫碳同位素比值(Nps-δ^(13)C)的变化发现,生物硅含量在末次冰消期较高,在约16 ka B.P.达到极大值,这指示了冰消期罗斯海海域深层水上涌增强并在约16 ka B.P.最为剧烈。与此同时,Nps-δ^(13)C的负偏,指示了南大洋上涌的水团将溶解的硅酸盐传递至海洋表层的同时,也将碳同位素等化学信号传递至表层海水。深层水上涌在末次冰消期显著增强的趋势,与大气CO_(2)浓度在冰消期之后的急剧上升十分吻合,这进一步验证了冰消期南大洋深层水上涌的假说及其对大气CO_(2)浓度上升的贡献。此外,本研究进一步讨论了引起末次冰消期南大洋深层水上涌的可能触发机制,主要可能因南北两极热量分布不均,导致南半球西风带位置和强度以及大西洋经向翻转流强度发生变化,进而驱动南大洋深层水上涌。
Polymers with excellent dielectric and electret capabilities are crucial for energy storage films, organic electronics and environmental filtrations. Nanocomposites is an emerging effective method, but the characteris...
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