title: T-cell autophagy deficiency increases mortality and suppresses immune responses after sepsis.
abstract: BACKGROUND
  Although the role of autophagy in sepsis has been characterized in several organs, its role in the adaptive immune system remains to be ascertained. This study aimed to investigate the role of autophagy in sepsis-induced T cell apoptosis and immunosuppression, using knockout mice with T cell specific deletion of autophagy essential gene Atg7.
  
  
  RESULTS
  Sepsis was induced in a cecal ligation and puncture (CLP) model, with T-cell-specific Atg7-knockout mice compared to control mice. Autophagic vacuoles examined by electron microscopy were decreased in the spleen after CLP. Autophagy proteins LC3-II and ATG7, and autophagosomes and autolysosomes stained by Cyto-ID Green and acridine orange were decreased in CD4+ and CD8+ splenocytes at 18 h and 24 h after CLP. This decrease in autophagy was associated with increased apoptosis of CD4+ and CD8+ after CLP. Moreover, mice lacking Atg7 in T lymphocytes showed an increase in sepsis-induced mortality, T cell apoptosis and loss of CD4+ and CD8+ T cells, in comparison to control mice. This was accompanied by suppressed cytokine production of Th1/Th2/Th17 by CD4+ T cells, reduced phagocytosis in macrophages and decreased bacterial clearance in the spleen after sepsis.
  
  
  CONCLUSIONS
  These results indicated that sepsis led to down-regulation of autophagy in T lymphocytes, which may result in enhanced apoptosis induction and decreased survival in sepsis. Autophagy may therefore play a protective role against sepsis-induced T lymphocyte apoptosis and immunosuppression.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Plastic and Reconstructive Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Canniesburn Plastic Surgery Unit, Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Steven
authors.initials: S
authors.lastname: Lo
authors.affiliation: Department of Physiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chin
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Department of Surgery, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Surgery, Benq Medical Center at Suzhou, Suzhou, China.
authors.forename: Chi-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Bao-Sheng
authors.initials: BS
authors.lastname: Hou
authors.affiliation: Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.affiliation: Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Gueishan, Taiwan.
authors.forename: Chih-Che
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Ming-Lung
authors.initials: ML
authors.lastname: Yu
authors.affiliation: Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Translational Research Center and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Obstetrics & Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Shyng-Shiou
authors.initials: SS
authors.lastname: Yuan
authors.affiliation: Department of Medical Research, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Ya-Ching
authors.initials: YC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001343:Autophagy / Q000276:immunology*; D000071193:Autophagy-Related Protein 7; D002432:Cecum / Q000601:surgery; D016207:Cytokines / Q000096:biosynthesis; D055786:Gene Knockout Techniques; D008026:Ligation / Q000009:adverse effects; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D010587:Phagocytosis; D011677:Punctures / Q000009:adverse effects; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000401:mortality*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: C502661:Atg7 protein, mouse; D016207:Cytokines; D008869:Microtubule-Associated Proteins; D000071193:Autophagy-Related Protein 7