Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection.
Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection.
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DOI：
10.1016/j.cell.2011.08.015
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发表时间：
2011-09-16
期刊：
影响因子：
64.5
通讯作者：
Rosen H
中科院分区：
文献类型：
--
作者：
Teijaro JR;Walsh KB;Cahalan S;Fremgen DM;Roberts E;Scott F;Martinborough E;Peach R;Oldstone MB;Rosen H
Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P1 receptor, we elucidate cellular and signaling mechanisms that are important in initiating cytokine storm. Whereas S1P1 receptor is expressed on endothelial cells and lymphocytes within lung tissue, S1P1 agonism suppresses cytokines and innate immune cell recruitment in wild-type and lymphocyte-deficient mice, identifying endothelial cells as central regulators of cytokine storm. Furthermore, our data reveal immune cell infiltration and cytokine production as distinct events that are both orchestrated by endothelial cells. Moreover, we demonstrate that suppression of early innate immune responses through S1P1 signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus. Modulation of endothelium with a specific agonist suggests that diseases in which amplification of cytokine storm is a significant pathological component could be chemically tractable. ► S1P1 signaling inhibits cytokine storms, potentially fatal immune responses ► S1P1 signaling in the endothelium protects mice from pathogenic human influenza ► In cytokine storms, cytokine production and leukocyte recruitment are separate events ► S1P1 signaling suppresses chemokine production by pulmonary endothelial cells The common flu virus can trigger potentially fatal immune reactions. In a surprising new role, endothelial cells of the lung express a potentially targetable receptor that suppresses this response.
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影响因子：
64.8
作者：
Kobasa, D;Takada, A;Kawaoka, Y
通讯作者：
Kawaoka, Y
DOI：
10.1186/cc8208
发表时间：
2009
期刊：
Critical care (London, England)
影响因子：
--
作者：
Bermejo-Martin JF;Ortiz de Lejarazu R;Pumarola T;Rello J;Almansa R;Ramírez P;Martin-Loeches I;Varillas D;Gallegos MC;Serón C;Micheloud D;Gomez JM;Tenorio-Abreu A;Ramos MJ;Molina ML;Huidobro S;Sanchez E;Gordón M;Fernández V;Del Castillo A;Marcos MA;Villanueva B;López CJ;Rodríguez-Domínguez M;Galan JC;Cantón R;Lietor A;Rojo S;Eiros JM;Hinojosa C;Gonzalez I;Torner N;Banner D;Leon A;Cuesta P;Rowe T;Kelvin DJ
通讯作者：
Kelvin DJ
影响因子：
3.6
作者：
Gonzalez-Cabrera PJ;Jo E;Sanna MG;Brown S;Leaf N;Marsolais D;Schaeffer MT;Chapman J;Cameron M;Guerrero M;Roberts E;Rosen H
通讯作者：
Rosen H
影响因子：
64.8
作者：
Kobasa, Darwyn;Jones, Steven M.;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
影响因子：
12.7
作者：
Kaiser, L;Fritz, RS;Hayden, FG
通讯作者：
Hayden, FG