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

Francisco A. Sylvester, Andrew Draghi, Antoine Menoret, Marina L. Fernandez, Zhu Wang, Anthony T. Vella

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)553-561
Number of pages9
JournalJournal of Pediatric Gastroenterology and Nutrition
Issue number5
StatePublished - Nov 8 2014
Externally publishedYes


  • Children
  • Colon
  • Crohn disease
  • Immune responses
  • Inflammatory bowel disease
  • Innate

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology


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