NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD

Raffaella La Scaleia, Antonella Stoppacciaro, Salvatore Oliva, Stefania Morrone, Giovanni Di Nardo, Angela Santoni, Salvatore Cucchiara, Gabriella Palmieri

Research output: Contribution to journalArticlepeer-review

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. (Inflamm Bowel Dis 2012)

Original languageEnglish
Pages (from-to)1910-1922
Number of pages13
JournalInflammatory Bowel Diseases
Volume18
Issue number10
DOIs
Publication statusPublished - Oct 2012

Keywords

  • γ/δ T cells
  • CD56+ T cells
  • MIC-A/B
  • ULBPs

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

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