Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19.
Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19.
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在致命的Covid-19中，与年龄相关风险和肺泡损伤的免疫和上皮决定因素。
DOI：
10.1172/jci.insight.157608
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发表时间：
2022-06-08
期刊：
影响因子：
8
通讯作者：
Weisberg, Stuart P.
中科院分区：
文献类型：
--
作者：
Chait, Michael;Yilmaz, Mine M.;Shakil, Shanila;Ku, Amy W.;Dogra, Pranay;Connors, Thomas J.;Szabo, Peter A.;Gray, Joshua I.;Wells, Steven B.;Kubota, Masaru;Matsumoto, Rei;Poon, Maya M. L.;Snyder, Mark E.;Baldwin, Matthew R.;Sims, Peter A.;Saqi, Anjali;Farber, Donna L.;Weisberg, Stuart P.
新冠肺炎患者的呼吸衰竭的特点是肺泡气体交换界面广泛中断。为了阐明肺泡损伤的决定因素，我们对24例新冠肺炎尸检和43例18-92岁未感染的器官捐赠者的肺进行了上皮细胞和免疫细胞分析。我们发现，在所有致命性新冠肺炎病例中，甚至在典型的急性肺损伤组织学明显之前的早期，2型肺泡上皮(T2AE)细胞显著丧失，肺泡周围淋巴细胞的细胞毒作用增强。在未感染的器官捐赠者的肺中，随着年龄的增长，T2AE细胞也逐渐丧失，这可能增加了老年人对新冠肺炎介导的肺损伤的易感性。在致命性新冠肺炎病例中，肺损伤的组织病理类型不同，巨噬细胞的浸润也不同。在急性肺损伤的病例中，我们发现CD4+巨噬细胞聚集，明显表达高水平的T细胞激活和共刺激基因，并与肺泡上皮细胞耗竭程度和CD8+T细胞杀伤作用的增加密切相关。总之，我们的结果表明，T2AE细胞缺陷可能是年龄相关新冠肺炎风险的基础，并在感染后不久引发肺泡功能障碍，我们定义了在致命性新冠肺炎的不同病理阶段可能导致肺泡损伤的免疫细胞介质。
Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18–92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19–mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.
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影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.8
作者：
Delorey TM;Ziegler CGK;Heimberg G;Normand R;Yang Y;Segerstolpe Å;Abbondanza D;Fleming SJ;Subramanian A;Montoro DT;Jagadeesh KA;Dey KK;Sen P;Slyper M;Pita-Juárez YH;Phillips D;Biermann J;Bloom-Ackermann Z;Barkas N;Ganna A;Gomez J;Melms JC;Katsyv I;Normandin E;Naderi P;Popov YV;Raju SS;Niezen S;Tsai LT;Siddle KJ;Sud M;Tran VM;Vellarikkal SK;Wang Y;Amir-Zilberstein L;Atri DS;Beechem J;Brook OR;Chen J;Divakar P;Dorceus P;Engreitz JM;Essene A;Fitzgerald DM;Fropf R;Gazal S;Gould J;Grzyb J;Harvey T;Hecht J;Hether T;Jané-Valbuena J;Leney-Greene M;Ma H;McCabe C;McLoughlin DE;Miller EM;Muus C;Niemi M;Padera R;Pan L;Pant D;Pe'er C;Pfiffner-Borges J;Pinto CJ;Plaisted J;Reeves J;Ross M;Rudy M;Rueckert EH;Siciliano M;Sturm A;Todres E;Waghray A;Warren S;Zhang S;Zollinger DR;Cosimi L;Gupta RM;Hacohen N;Hibshoosh H;Hide W;Price AL;Rajagopal J;Tata PR;Riedel S;Szabo G;Tickle TL;Ellinor PT;Hung D;Sabeti PC;Novak R;Rogers R;Ingber DE;Jiang ZG;Juric D;Babadi M;Farhi SL;Izar B;Stone JR;Vlachos IS;Solomon IH;Ashenberg O;Porter CBM;Li B;Shalek AK;Villani AC;Rozenblatt-Rosen O;Regev A
通讯作者：
Regev A
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
DOI：
10.1111/j.1349-7006.2000.tb00879.x
发表时间：
2000-10
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Hirano T;Auer G;Maeda M;Hagiwara Y;Okada S;Ohira T;Okuzawa K;Fujioka K;Franzén B;Hibi N;Seito T;Ebihara Y;Kato H
通讯作者：
Kato H