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Pediatric Crohn disease is characterized by Th1 in the terminal ileum and Th1/Th17 immune response in the colon

Abstract

The aim of this study was to assess the expression of inflammatory mediators in the affected terminal ileum and colon in pediatric Crohn disease (CD) patients with different stages of disease. Additionally, we assessed the role of efflux transporters in disease pathogenesis and their correlation with immune response. The study included 26 CD patients (10 newly diagnosed (CD-new), 8 CD-treated, and 8 CD-remission) and 15 control subjects. The terminal ileum IFN-γ, IL-6, and IL-1β were elevated in CD-new, while in the colon, the IFN-γ, IL-17A, and IL-6 were elevated in both CD-new and CD-treated subgroups. SOCS3 expression was elevated in both subgroups with active inflammation at both ileum and colon, while SOCS1 was elevated only in CD-new ileum and CD-treated colon. MDR1 expression in ileum was reduced in both subgroups with active inflammation, while BCRP was reduced only in CD-new subgroup.

Conclusion: New onset pediatric CD is characterized by Th1 response in ileum and mixed Th1/Th17 response in the colon, with elevated expressions of innate IL-6 and IL-1β. SOCS1/SOCS3 expressions seem to be insufficient for the regulation of the immune response. The reduction in MDR1 expression points to its role in the disease pathogenesis.

What is Known:
CD is characterized by an aberrant immune response
What is New:
The immune response in new onset pediatric CD differs between terminal ileum and colon
MDR1 expression is downregulated at both terminal ileum and colon irrespective of the disease activity

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Abbreviations

BCRP:

Breast cancer resistance protein

CD:

Crohn disease

CRP:

C-reactive protein

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

IBD:

Inflammatory bowel disease

IFN:

Interferon

IL:

Interleukin

MDR1:

Multidrug resistance gene

MRP1:

Multidrug resistance-associated protein 1

NF-κB:

Nuclear factor-κB

PCDAI:

Pediatric Crohn Disease Activity Index

SOCS:

Suppressors of cytokine signaling molecules

STAT:

Signal transducer and activator of transcription

Treg :

Regulatory T cells

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Funding

This study was supported by the Croatian Ministry of Sciences and Education.

Author information

ASM carried out the experiments, data analyses and wrote and drafted the manuscript. IH provided the samples and revised the manuscript. MJ carried out parts of the experiments. SČ performed the statistical analysis. KB conceived and participated in the study and also helped drafting the manuscript. All authors read and approved the final manuscript.

Correspondence to Ana Savić Mlakar.

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Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by Peter de Winter

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Cite this article

Savić Mlakar, A., Hojsak, I., Jergović, M. et al. Pediatric Crohn disease is characterized by Th1 in the terminal ileum and Th1/Th17 immune response in the colon. Eur J Pediatr 177, 611–616 (2018). https://doi.org/10.1007/s00431-017-3076-8

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Keywords

  • Children
  • Crohn disease
  • Immune response
  • SOCS molecules
  • Efflux transporters