title: Alteration of intestinal epithelial function by intraepithelial lymphocyte homing.
abstract: BACKGROUND
  Intimate cross-talk may take place between intestinal epithelial cells and intraepithelial lymphocytes (IEL). The purpose of this study was to analyze the influence of lymphocyte migration into the epithelium on epithelial function, using an in vitro "IEL homing" model.
  
  
  METHODS
  Molecular expression on epithelial cells was analyzed by flow cytometry. The barrier function of the epithelial monolayer was assessed by transepithelial electrical resistance. Cytokine production was measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  (1) IEL homing into the epithelia induced significant phenotypic changes in epithelial cells; upregulation of MHC class I, and II, intercellular adhesion molecule (ICAM)-1, and CD44. IEL-derived interferon-gamma (IFN-gamma) could partially account for this alteration, as a neutralizing antibody (Ab) against IFN-gamma inhibited the upregulation of these molecules, except for CD44. (2) A marked fall in transepithelial electrical resistance was observed 4 h after IEL homing started, and Ab against IFN-gamma slightly inhibited this fall in resistance. (3) The production of interleukin (IL)-8 and IFN-gamma inducible protein-10 (IP-10), but not transforming growth factor (TGF)-beta1 or tumor necrosis factor (TNF)-alpha, in the epithelial monolayer was markedly induced after IEL homing in a basolaterally polarized fashion. IEL-conditioned media also induced the production of these cytokines in epithelial cells, thus suggesting that IEL-derived soluble factor(s) induce epithelial chemokine production.
  
  
  CONCLUSIONS
  Under inflammatory conditions, IEL obviously interact with epithelial cells and upregulate adhesion molecules, alter barrier function, and enhance chemokine production. Because such alterations may increase epithelial permeability to luminal antigens or accelerate the migration of other inflammatory cells, our results suggest that IEL have a critical role in mucosal immunity.
authors.affiliation: Department of Gastroenterology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8575, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shibahara
authors.forename: Kaori
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Matsui
authors.forename: Akinori
authors.initials: A
authors.lastname: Yanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Nakahara
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016201:Receptors, Lymphocyte Homing