Abstract
Heat shock proteins (HSPs) are essential mediators of cellular homeostasis by maintaining protein functionality and stability, and activating appropriate immune cells. HSP activity is influenced by a variety of factors including diet, microbial stimuli, environment and host immunity. The overexpression and down-regulation of HSPs is associated with various disease phenotypes, including the inflammatory bowel diseases (IBD) such as Crohn’s disease (CD). While the precise etiology of CD remains unclear, many of the putative triggers also influence HSP activity. The development of different CD phenotypes therefore may be a result of the disease-modifying behavior of the environmentally-regulated HSPs. Understanding the role of bacterial and endogenous HSPs in host homeostasis and disease will help elucidate the complex interplay of factors. Furthermore, discerning the function of HSPs in CD may lead to therapeutic developments that better reflect and respond to the gut environment.
Highlights
Crohn’s disease (CD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract and a major form of inflammatory bowel disease (IBD)
Intestinal epithelial cells play an active role in maintaining immune homeostasis by forming a barrier between the underlying tissues and the microbe-rich luminal environment [3]
There is an expanding group of genes involved in monogenic IBD that are associated with significant intestinal epithelial barrier dysfunction [5]
Summary
Crohn’s disease (CD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract and a major form of inflammatory bowel disease (IBD). Intestinal epithelial cells play an active role in maintaining immune homeostasis by forming a barrier between the underlying tissues and the microbe-rich luminal environment [3]. The ≥200 susceptibility loci identified to date account for only 26% of CD variance [6] This “missing heritability” in turn is determined by an estimation of genetic risk based on twin concordance studies, variants associated with gene expression regulation rather than protein-altering variants, and a gene–environment/microbiome interaction that has proven difficult to model without a better understanding of environmental triggers [7,8,9,10]. Endogenous heat shock proteins (HSPs) represent a major mechanism for protecting intestinal epithelial cell function and viability against a variety of environmental and physiological stressors. We review the current understanding of HSPs in mediating host inflammatory responses in CD, and we describe ongoing studies of bacterial HSPs in CD pathogenesis and protection
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