The innate immune system and inflammatory bowel disease

Abstract

The innate immune system is a key factor in understanding the pathogenesis of inflammatory bowel disease (IBD) and in the hopes of improving its treatment. NOD2, a pattern recognition receptor, was one of the first major susceptibility genes identified in Crohn’s disease (CD). This discovery has been followed by genome-wide association studies that have identified other genes involved in innate immune responses. Most notably, polymorphisms in the interleukin (IL)-23 receptor have also been linked to IBD – both CD and ulcerative colitis. At the core of the innate immune defects associated with IBD is a lack of generating a robust response to control invasive commensal or pathogenic bacteria. The defect sometimes lies in a failure of the epithelium to express antimicrobial peptides or in defective control of intracellular bacteria by phagocytic cells such as dendritic cells, macrophages, or neutrophils. The recent identification of innate lymphoid cells that express the IL-23 receptor and generate both proinflammatory and protective or regulatory responses to commensal or pathogenic bacteria provides another layer of complexity to the interplay of host protection and dysregulated inflammation. Although inhibition of tumor necrosis factor has been highly successful as a strategy in treating IBD, we must better understand the nuanced role of other innate cytokines before we may incorporate these in the treatment of IBD.

Key Words:

• Crohn’s disease
• dendritic cells
• interleukin-17
• interleukin-23
• inflammatory bowel disease
• innate lymphoid cells
• NOD-like receptors
• pattern recognition receptors
• Toll-like receptors
• ulcerative colitis

Acknowledgments

Funding for this review was provided by grants to support the laboratory of MTA (National Institute of Health, National Cancer Institute 5R01CA137869-05, National Institute of Diabetes and Digestive and Kidney Diseases 2R01DK099076-06A1, Crohn’s and Colitis Foundation of America Senior Investigator Award).

Declaration of interest: The authors have read the journal’s policy and have the following competing interests: MT Abreu has served as a consultant to Abbott Laboratories, Bristol-Myers Squibb, Hospira, Merck, Pfizer, Sanofi-Aventis, Janssen, GSK Holding Americas, Inc., and UCB.