Pediatric Inflammatory Bowel Disease: A Review of Immune Homeostasis and Genetics with an Emphasis on the IL-10 Pathway

Tony R Lin¹, Joanna Floros^2,3 and Zhenwu Lin⁴*

Received: January 17, 2018;   Published: January 31, 2018

DOI: 10.26717/BJSTR.2018.02.000713

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Abstract

Inflammatory bowel disease (IBD) is an auto-immune condition characterized by chronic gastrointestinal inflammation. The incidence of pediatric IBD, particularly the early onset disease subtypes, has been increasing internationally. In contrast to later-onset IBD, recent literature indicates that early-onset (between 3 - 5 years) and very early-onset (between 0 - 2 years) patients present with a more severe and aggressive disease. A comprehensive review of the literature indicates that the gut microbiome, which is heavily influenced in the early life, is reduced in IBD patients and hence plays a role in regulating gastrointestinal homeostasis. While many genes have been confirmed to be associated with IBD, only a portion of those genes have been shown to cause pediatric IBD.

The IL-10/STAT3 pathway is a well-studied gene pathway as is, involved in maintaining immune homeostasis in both acute and chronic inflammation. Accumulating evidence indicates that IL-10/STAT3 pathway is a key player in pediatric IBD. New mutations identified within the IL-10 pathway have been shown to disrupt immune homeostasis and cause gastrointestinal inflammation. Furthermore, significant epistatic interactions have been demonstrated between different single-nucleotide polymorphisms of IL-10 genes suggesting that understanding gene interactions within the IL-10//STAT3 pathway may be key to understanding more about IBD pathogenesis. Heme oxygenase 1 (HO-1) is speculated to be regulated by the IL-10/STAT3 pathway and hence involved in pediatric IBD formation. This review aims to provide an overview of pediatric IBD and discuss the role of the gut microbiome, IL-10/STAT3 pathway, and HO-1 gene in modulating immune homeostasis in IBD pathogenesis.

Key words: Inflammatory bowel disease; Crohn’s disease; Ulcerative colitis; Pediatric; Early onset; Very early-onset; IL-10, STAT3; HO-1

Abbreviations: IBD: Inflammatory Bowel Disease; UC: Ulcerative Colitis; CD: Crohn’s Disease; NVDW: Neutrophil Volume Distribution width; PCDAI: Pediatric Crohn’s Disease Activity Index;

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