title: Imbalance of NKp44(+)NKp46(-) and NKp44(-)NKp46(+) natural killer cells in the intestinal mucosa of patients with Crohn's disease.
abstract: OBJECTIVE
  Mucosal natural killer (NK) cells that produce interleukin (IL)-22 mediate intestinal homeostasis and inflammation in mice. However, their role in the pathogenesis of human inflammatory bowel diseases (IBDs) is not known. We investigated intestinal NK cells in intestinal mucosa samples of patients with Crohn's disease (CD).
  
  
  METHODS
  We isolated lamina propria NK cells from intestinal mucosal samples of patients with IBD and subjects without IBD (controls) and analyzed expression patterns of cell surface molecules and cytokine production. Interactions between lamina propria NK cells and intestinal macrophages were examined.
  
  
  RESULTS
  In intestinal mucosa samples from controls, NKp44 and NKp46 were expressed differentially on CD3(-)CD56(+) NK cells, NKp44(+)NKp46(-) (NKp44(+)) NK cells expressed CD127 and the transcription factor retinoic acid-related orphan receptor C (RORC) and produced IL-22 whereas NKp44(-)NKp46(+) (NKp46(+)) NK cells did not express CD127 or RORC and produced interferon (IFN)-gamma. NKp46(+) NK cells were predominant in intestinal mucosa of patients with CD compared with controls or patients with ulcerative colitis. Upon interaction with intestinal inflammatory macrophages NKp46(+), NK cells from patients with CD were activated via IL-23 and produced IFN-gamma; this activation required cell-to-cell contact.
  
  
  CONCLUSIONS
  The balance of NKp44(+)/NKp46(+) NK cells is disrupted in intestinal mucosa of patients with CD. NKp46(+) NK cells might mediate the pathogenesis of CD by producing IFN-gamma.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takayama
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Chinen
authors.forename: Susumu
authors.initials: S
authors.lastname: Okamoto
authors.forename: Mina T
authors.initials: MT
authors.lastname: Kitazume
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.forename: Yumi
authors.initials: Y
authors.lastname: Matuzaki
authors.forename: Sadafumi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Sugita
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Koganei
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Hisamatsu
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D013293:Enterococcus faecalis / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007420:Intestine, Large / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D007371:Interferon-gamma; D053759:Interleukin-23; D053699:Interleukin-7 Receptor alpha Subunit; D007378:Interleukins; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D000097043:Interleukin-22; C112260:NCR1 protein, human; C112837:NCR2 protein, human; C539900:RORC protein, human; C117026:TNFSF15 protein, human