Abstract
Inflammatory disorders of the gastro-intestinal tract are a major cause of morbidity and significant burden from a health and economic perspective in industrialized countries. While the incidence of such conditions has a strong environmental component, in particular dietary composition, epidemiological studies have identified specific hereditary mutations which result in disequilibrium between pro- and anti-inflammatory factors. The IL-1 super-family of cytokines and receptors is highly pleiotropic and plays a fundamental role in the pathogenesis of several auto-inflammatory conditions including rheumatoid arthritis, multiple sclerosis and psoriasis. However, the role of this super-family in the etiology of inflammatory bowel diseases remains incompletely resolved despite extensive research. Herein, we highlight the currently accepted paradigms as they pertain to specific IL-1 family members and focus on some recently described non-classical roles for these pathways in the gastrointestinal tract. Finally, we address some of the shortcomings and sources of variance in the field which to date have yielded several conflicting results from similar studies and discuss the potential effect of these factors on data interpretation.
Highlights
In addition to these classical pro-inflammatory functions, several IL-1 family cytokines are capable of modulating downstream effector T cell responses by directing their differentiation down different pathways
Reviewed by: Ruaidhri Carmody, University of Glasgow, United Kingdom Aldo Tagliabue, Institute for Genetic and Biomedical Research (IRGB), Italy
While distinct regions of the gastrointestinal tract (GIT) differ in terms of their anatomical, physiological and immunological make-up, consistent throughout is the presence of a single layer of columnar intestinal epithelial cells (IECs) which act as a physical blockade between the luminal compartment and the typically sterile underlying sub-epithelial layers [1]
Summary
In addition to these classical pro-inflammatory functions, several IL-1 family cytokines are capable of modulating downstream effector T cell responses by directing their differentiation down different pathways. This receptor appears to be of particular importance in the GIT as both IECs and intestinal DCs from SIGIRR-deficient mice exhibit a skewed immunological profile characterized by a constitutive up-regulation of inflammatory genes and enhanced responsiveness to TLR ligands.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call