title: NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD.
abstract: BACKGROUND
  Dysregulated innate immune responses play an important role in inflammatory bowel disease (IBD). NKG2D innate immunity receptor is a major sensor of tissue damage that, by recognizing multiple stress-induced, cell-associated ligands (MIC-A/B and ULBP1-5), potentiates the effector functions of "innate-like" (γ/δ TcR+, and natural killer receptor+ [NKR+]) T-cell populations. We analyzed the representivity, NKG2D/ligand expression pattern, and functional ability of the major innate immunity cell populations in pediatric IBD patients.
  
  
  METHODS
  We analyzed 41 Crohn's disease (CD) patients, 33 ulcerative colitis (UC) patients, and 51 age-matched non-IBD controls. The expression of NKG2D and its ligands, interferon-gamma (IFN-γ) production, and cytotoxic granule release were assessed by immunostaining and multiparameter cytofluorimetric analysis on circulating and mucosal mononuclear subsets; the inflammatory infiltrate was also characterized by immunohistochemistry.
  
  
  RESULTS
  The expression pattern of NKG2D receptor and its ligands on mucosal and circulating innate immunity populations is severely disturbed in IBD; NKG2D and ligands are upregulated on immune infiltrate in both CD and UC active lesions; receptor/ligand upregulation also occurs on circulating leukocyte populations, where it depends on both disease activity and type (UC vs. CD). Finally, the frequency and effector capability of peripheral blood "innate-like" T-cell populations are also altered in IBD patients.
  
  
  CONCLUSIONS
  The circulating and mucosal innate immunity compartment is phenotypically and functionally altered in pediatric IBD; some alterations may represent a distinctive feature of the pediatric disease condition. The disturbance of NKG2D/ligand pathway may play a role in sustaining immune activation which leads to chronic inflammatory tissue damage.
authors.affiliation: Department of Experimental Medicine, La Sapienza, University of Rome, Rome, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: La Scaleia
authors.forename: Antonella
authors.initials: A
authors.lastname: Stoppacciaro
authors.forename: Salvatore
authors.initials: S
authors.lastname: Oliva
authors.forename: Stefania
authors.initials: S
authors.lastname: Morrone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Nardo
authors.forename: Angela
authors.initials: A
authors.lastname: Santoni
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.forename: Gabriella
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003424:Crohn Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011379:Prognosis; D012307:Risk Factors; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
chemical_list: D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D007371:Interferon-gamma