V gamma 4+gamma delta T Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A
单位：[1]Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China,[2]Department of Immunology, The Research Centre of Microbiome, School of Basic Medical Sciences, Capital Medical University, Beijing, China,[3]Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China,[4]Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China,[5]Department of Pulmonary and Critical Care Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing, China,[6]Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Beijing, China,[7]Department of Respiratory Medicine, Capital Medical University, Beijing, China
The influenza A (H1N1) pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the major outcomes among severely infected patients. Our previous study found that interleukin (IL)-17A production by humans or mice infected with influenza A (H1N1) pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1) pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1) pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of gamma delta T cells, but not the percentages of CD4(+)Th and CD8(+)Tc cells, gradually increased and peaked at 3 days post-infection (dpi). Further analysis revealed that the V gamma 4+gamma delta T subset, but not the V gamma 1+gamma delta T subset, was significantly increased among the gamma delta T cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF) and serum. IL-17A was predominantly secreted by gamma delta T cells (especially the V gamma 4+gamma delta T subset), but not CD4(+)Th and CD8(+)Tc cells at the early stage of infection, and IL-1 beta and/or IL-23 were sufficient to induce IL-17A production by gamma delta T cells. In addition to secreting IL-17A, gamma delta T cells secreted interferon (IFN)-gamma and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D), and an apoptosis-associated molecule, FasL. Depletion of gamma delta T cells or the V gamma 4+gamma delta T subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung V gamma 4+gamma delta T cells, at least, in part mediated influenza A (H1N1) pdm09-induced immunopathological injury. This mechanism might serve as a promising new target for the prevention and treatment of ALI induced by influenza A (H1N1) pdm09.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81425001/H0104, 81271840, 81373114]; Beijing Municipal Natural Science FoundationBeijing Natural Science Foundation [7132072]; National Key Technology Support Program of the Ministry of Science and Technology [2015BAI12B11]; Beijing Science and Technology Project [D151100002115004]
第一作者单位：[1]Department of Respiratory and Critical Care Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, China,
共同第一作者：
通讯作者：
通讯机构：[4]Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China,[6]Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Beijing, China,[7]Department of Respiratory Medicine, Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Xue Chunxue,Wen Mingjie,Bao Linlin,et al.V gamma 4+gamma delta T Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A[J].FRONTIERS in IMMUNOLOGY.2017,8:doi:10.3389/fimmu.2017.01054.
APA：
Xue, Chunxue,Wen, Mingjie,Bao, Linlin,Li, Hui,Li, Fengdi...&Cao, Bin.(2017).V gamma 4+gamma delta T Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A.FRONTIERS in IMMUNOLOGY,8,
MLA：
Xue, Chunxue,et al."V gamma 4+gamma delta T Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A".FRONTIERS in IMMUNOLOGY 8.(2017)
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