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J Pediatr Gastroenterol Nutr. 2014 Nov;59(5):553-61. doi: 10.1097/MPG.0000000000000480.

Distinctive colonic mucosal cytokine signature in new-onset, untreated pediatric Crohn disease.

Author information

1
*Department of Pediatrics, Connecticut Children's Medical Center, Hartford †Department of Immunology, University of Connecticut Health Center, Farmington.

Abstract

OBJECTIVE:

The aim of the study was to compare the colonic mucosal immune response in children with new, untreated Crohn disease (CD-New), CD in remission (CD-Remission), and unaffected children (CTRL [controls]).

METHODS:

We performed flow cytometry of mitogen-stimulated colonic lamina propria mononuclear cells isolated from colonic biopsies and 72-hour biopsy explant cultures, and analyzed the supernatant by an unbiased multiplex cytokine array of 45 analytes.

RESULTS:

Thirty-six children were studied (mean age 14 ± 3 years, 14 girls): 12 CD-New, 11 CD-Remission, and 13 CTRL. We found that stimulation of lamina propria mononuclear cells isolated from colonic biopsies induced comparable intracellular cytokine levels of interferon (IFN-γ), interleukin (IL)-17, and tumor necrosis factor (TNF)-α in T cells from CD-New, CD-Remission, and CTRL, suggesting that mucosal innate inflammation plays a larger role than activated T cells in CD-New. To measure factors released during the ongoing inflammatory response in CD-New, we cultured colonic biopsy explants and uncovered 13/45 factors that were significantly higher in CD-New versus CD-Remission, whereas 10 were increased in CD-New over CTRL. Ingenuity Pathway Analysis software revealed the anticipated interconnectivity of TNF-α, IL-6, and CSF-2 in CD-New of the colon. A novel subnetwork of chemokines was, however, evident, whereas IL-17a appeared as a peripheral factor. Principal component analysis and hierarchal clustering showed that CD-New and CD-Remission separated into distinct subgroups based on the 13 factors.

CONCLUSIONS:

At diagnosis of inflammatory bowel disease, the colonic cytokine response contains a predominance of innate immune factors, with chemoattractants and vascular adhesion molecules playing a central role.

PMID:
25000355
DOI:
10.1097/MPG.0000000000000480
[Indexed for MEDLINE]

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