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 language | English |
|---|---|
| Pages (from-to) | 1910-1922 |
| Number of pages | 13 |
| Journal | Inflammatory Bowel Diseases |
| Volume | 18 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2012 |
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Keywords
- γ/δ T cells
- CD56+ T cells
- MIC-A/B
- ULBPs
ASJC Scopus subject areas
- Gastroenterology
- Immunology and Allergy
Cite this
NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD. / La Scaleia, Raffaella; Stoppacciaro, Antonella; Oliva, Salvatore; Morrone, Stefania; Di Nardo, Giovanni; Santoni, Angela; Cucchiara, Salvatore; Palmieri, Gabriella.
In: Inflammatory Bowel Diseases, Vol. 18, No. 10, 10.2012, p. 1910-1922.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NKG2D/Ligand dysregulation and functional alteration of innate immunity cell populations in pediatric IBD
AU - La Scaleia, Raffaella
AU - Stoppacciaro, Antonella
AU - Oliva, Salvatore
AU - Morrone, Stefania
AU - Di Nardo, Giovanni
AU - Santoni, Angela
AU - Cucchiara, Salvatore
AU - Palmieri, Gabriella
PY - 2012/10
Y1 - 2012/10
N2 - 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)
AB - 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)
KW - γ/δ T cells
KW - CD56+ T cells
KW - MIC-A/B
KW - ULBPs
UR - http://www.scopus.com/inward/record.url?scp=84866391640&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866391640&partnerID=8YFLogxK
U2 - 10.1002/ibd.22899
DO - 10.1002/ibd.22899
M3 - Article
C2 - 22294522
AN - SCOPUS:84866391640
VL - 18
SP - 1910
EP - 1922
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 10
ER -