The Role of Human Defensins in Gastrointestinal Diseases

Jost Langhorst; Kyung-Eun Choi


Expert Rev Clin Immunol. 2011;7(6):779-787. 

In This Article

Expert Commentary & Five-year View

The exponentially growing knowledge of AMPs and their role in innate immunity has added important new aspects to the current understanding of IBD. Several studies have highlighted the relevance of innate immunity besides dysregulations of adaptive immune responses for these diseases. Among the different types of molecules that are involved in the innate defense system, defensins have been shown to play a crucial role. While changes of AMP expression are a biological reaction to inflammation and/or reflux of bacteria, other changes are independent of inflammation status. This depends on disease phenotype, location and is different for different antimicrobials.

The next years will certainly involve the investigation of susceptibility genes of IBD as well as identifying clear expression patterns of all defensins due to proinflammatory and/or protective bacteria in patients concerned. Herein, from a clinical point of view, the investigation of defensins with corresponding cytokine-profiles and bacterial flora will be of major importance. For basic research, further exploration into signal transduction pathways and favourable environments responsible for regulating defensins' expression is certainly required, which might open the door for defensins as potential noninvasive biomarkers for these diseases. Promising candidates are Paneth cells and Wnt signaling, as is the role of oxygen-rich versus reduced environments.

Since IBS was recently related to innate immune responses, this might even be a starting signal for re-evaluating IBS not as a commonly thought functional disorder with a diagnosis of exclusion within a psychosomatic model, but rather towards a yet unsatisfactorily described disease within a framework integrating biomarkers, animal models, psychoneuroimmunology and consequently more effective treatments. Concerning IBS, further analysis with respect to subgroups including gender or symptoms (e.g., diarrhea-predominant vs constipation-predominant IBS) in studies with large sample sizes could for example clarify the underlying connections. Prospectively assessed defensin levels in conjunction with the remission of symptoms might specifically elucidate the significance of defensins, innate immunity and that of possibly low-grade mucosal inflammation in IBS.

New insights in the pathophysiology of IBD and IBS will also clarify the significance of those concepts within a wider range, and possibly also other gastrointestinal diseases may benefit from that research. HBD-2 and other defensin levels may, for example, be investigated in gastrointestinal diseases with different pathophysiology such as celiac disease, lactose intolerance, food allergies and parasitic gastrointestinal diseases. Of course, further concepts such as environmental influence, smoking, diet and intestinal flora in the modulation of patients' susceptibility should not be neglected. This will open the door for a successful translation of research implications to clinical benefit.


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