title: Glutamine modulates CD8αα(+) TCRαβ(+) intestinal intraepithelial lymphocyte expression in mice with polymicrobial sepsis.
abstract: OBJECTIVE
  CD8αα(+) T-cell receptor (TCR) αβ(+) intestinal intraepithelial lymphocytes (IELs) were found to have a regulatory function in the mucosal immune system. Glutamine (GLN) is an amino acid with immunomodulatory effects. The aim of this study was to investigate the influences of GLN on the proportion of CD8αα(+) TCRαβ(+) IELs and associated inflammatory mediator gene expression in polymicrobial sepsis.
  
  
  METHODS
  Mice were randomly assigned to a normal (NC) group, a sepsis with saline (SS) group, or a sepsis with GLN (SG) group. The NC group was fed a chow diet. Sepsis was induced by cecal ligation and puncture (CLP). The SS group was administered saline, and the SG group was given 0.75 g GLN/kg body weight via a tail vein after CLP. Mice were sacrificed 12 h after CLP, and CD8αα(+) TCRαβ(+) IELs were isolated for further analysis.
  
  
  RESULTS
  Sepsis resulted in a lower percentage of CD8αα(+) TCRαβ(+) IELs, and higher messenger (m)RNA expression of complement 5a receptor, interleukin (IL)-2 receptor β, IL-15 receptor α, and interferon-γ by CD8αα(+) TCRαβ(+) IELs. These immunomodulatory mediator genes decreased, whereas IL-7 receptor and transforming growth factor-β expressions increased in CD8αα(+) TCRαβ(+) IELs in septic mice with GLN administration. Annexin V⁄7-AAD staining revealed significantly lower apoptotic rates of CD8αα(+) TCRαβ(+) IELs in the SG group.
  
  
  CONCLUSIONS
  A single dose of GLN administered after the initiation of sepsis increased the percentage of CD8αα(+) TCRαβ(+) IELs, prevented apoptosis of CD8αα(+) TCRαβ(+) IELs, and downregulated CD8αα(+) TCRαβ(+) IEL-expressed inflammatory mediators. These results suggest that GLN influenced the distribution and cytokine secretion of the CD8αα(+) TCRαβ(+) IEL subset, which may ameliorate sepsis-induced inflammatory reactions and thus mitigate the severity of intestinal epithelial injury.
authors.affiliation: Department of Surgery, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan.
authors.forename: Jai-Nien
authors.initials: JN
authors.lastname: Tung
authors.forename: Wan-Yun
authors.initials: WY
authors.lastname: Lee
authors.forename: Man-Hui
authors.initials: MH
authors.lastname: Pai
authors.forename: Wei-Jao
authors.initials: WJ
authors.lastname: Chen
authors.forename: Chiu-Li
authors.initials: CL
authors.lastname: Yeh
authors.forename: Sung-Ling
authors.initials: SL
authors.lastname: Yeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D005973:Glutamine / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D053720:Interleukin-15 Receptor alpha Subunit / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053720:Interleukin-15 Receptor alpha Subunit; D053583:Interleukin-1beta; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7; D005973:Glutamine; D007371:Interferon-gamma