title: Intraepithelial gammadelta+ lymphocytes maintain the integrity of intestinal epithelial tight junctions in response to infection.
abstract: OBJECTIVE
  Intestinal epithelial integrity and permeability is dependent on intercellular tight junction (TJ) complexes. How TJ integrity is regulated remains unclear, although phosphorylation and dephosphorylation of the integral membrane protein occludin is an important determinant of TJ formation and epithelial permeability. We have investigated the role intestinal intraepithelial lymphocytes (iIELs) play in regulating epithelial permeability in response to infection.
  
  
  METHODS
  Recombinant strains of Toxoplasma gondii were used to assess intestinal epithelial barrier function and TJ integrity in mice with intact or depleted populations of iIELs. Alterations in epithelial permeability were correlated with TJ structure and the state of phosphorylation of occludin. iIEL in vivo reconstitution experiments were used to identify the iIELs required to maintain epithelial permeability and TJ integrity.
  
  
  RESULTS
  In the absence of gammadelta+ iIELs, intestinal epithelial barrier function and the ability to restrict epithelial transmigration of Toxoplasma and the unrelated intracellular bacterial pathogen Salmonella typhimurium was severely compromised. Leaky epithelium in gammadelta+ iIEL-deficient mice was associated with the absence of phosphorylation of serine residues of occludin and lack of claudin 3 and zona occludens-1 proteins in TJ complexes. These deficiencies were attributable to the absence of a single subset of gammadelta T-cell receptor (TCR-Vgamma7+) iIELs that, after reconstituting gammadelta iIEL-deficient mice, restored epithelial barrier function and TJ complexes, resulting in increased resistance to infection.
  
  
  CONCLUSIONS
  These findings identify a novel role for gammadelta+ iIELs in maintaining TJ integrity and epithelial barrier function that have implications for understanding the pathogenesis of intestinal inflammatory diseases associated with disruption of TJ complexes.
authors.affiliation: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dalton
authors.forename: Sheena M
authors.initials: SM
authors.lastname: Cruickshank
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Egan
authors.forename: Rainy
authors.initials: R
authors.lastname: Mears
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Newton
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Andrew
authors.forename: Beth
authors.initials: B
authors.lastname: Lawrence
authors.forename: Gareth
authors.initials: G
authors.lastname: Howell
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Else
authors.forename: Marc-Jan
authors.initials: MJ
authors.lastname: Gubbels
authors.forename: Boris
authors.initials: B
authors.lastname: Striepen
authors.forename: Judith E
authors.initials: JE
authors.lastname: Smith
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: White
authors.forename: Simon R
authors.initials: SR
authors.lastname: Carding
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002463:Cell Membrane Permeability / Q000276:immunology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007365:Intercellular Junctions / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin; D010766:Phosphorylation; D012313:RNA / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014122:Toxoplasma / Q000302:isolation & purification / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012313:RNA