Their discovery in the human intestines came as quite a surprise – up until a few years ago, LTi – lymphoid tissue inducer - cells were only known to be involved in the embryonic development of the immune system. A team of researchers led by Prof. Dr. Andreas Diefenbach from the University of Freiburg Medical Centre has since been able to show the protective role played by LTi cells in fortifying the intestinal wall as a reaction to nutrients found in vegetables. Diefenbach has been awarded a European Research Council (ERC) Starting Grant to investigate the links between diet, cell biology and immune defense.
Phytochemicals are compounds occurring naturally in plants like broccoli, Brussels sprouts and mustard that have been found to have a positive effect on human health. But what are the effects of these phytochemicals - mustard oil glycosides or glucosinolates - on the human organism? A few years ago, Prof. Dr. Andreas Diefenbach and his team from the Innate Immune Recognition work group at the Institute of Medical Microbiology and Hygiene at the University of Freiburg Medical Centre came across the issue somewhat by accident. The immunologists were investigating a molecular switch that plays a role in the development of T helper cells in the immune system of mice. This switch, an Ah receptor (eds. note: Ah receptor: aryl hydrocarbon receptor), is found in many cell types, including so-called lymphoid tissue inducer cells (LTi cells), which control the development of immune system tissue (e.g. lymph nodes) during mammalian embryogenesis. “The receptor reacts to compounds found in food and in the environment,” Diefenbach said.
What happens when an environmental toxin or a broccoli ingredient interacts with the Ah receptor? The receptor protein is activated and migrates into the cell nucleus where genes that alter the behaviour of cells are transcribed in such a way that the cells are better able to adapt to changing environments. The activation of the receptor through environmental toxins (e.g. dioxins) leads to the activation of molecular detoxification cascades in the liver cells, amongst other things. And what happens in LTi cells? This is a question that was beginning to be asked more frequently in the light of a discovery made by Diefenbach’s team several years ago. The researchers discovered that LTi cells not only played a key role in embryonic processes, but also in post-embryonic processes, i.e. the development of so-called intestinal follicles. Intestinal follicles and lymph nodes have similar roles; i.e. they are sites of high immunological activity. Intestinal follicles are located in indentations of the intestinal wall and secrete different secondary metabolites which fortify the barrier function of intestinal epithelial cells against bacterial intruders.
“Our work on the Ah receptor was the starting point of our subsequent research into intestinal follicles,” explained Diefenbach. “For example, we found that the inactivation of the Ah receptor gene led to a reduction in the number of LTi cells in the intestines, and hence to a reduced ability to fight off bacteria,” Diefenbach added. The researchers from Freiburg now know that the Ah receptor is crucial for the maturation of LTi cells. The blockage or complete absence of Ah receptors reduces the number of LTi cells as well as preventing the formation of intestinal follicles. And this in turn prevents the intestinal wall from being able to effectively fight off bacteria. “We found that the composition of the intestinal flora changed,” said Diefenbach going on to add, “we found more bacterial species that trigger inflammation; the absence of LTi cells makes the intestines more susceptible to certain types of intestinal infections and inflammation.”
The processes in the intestinal follicles and their interactions with structures of the intestinal wall are highly complex. The researchers assume that in addition to LTi cells, stem cells and other immune system cell types (e.g. B lymphocytes) also play a role. Moreover, these processes involve numerous molecular mechanisms which Diefenbach and his group of researchers will study in greater detail over the next few years. And there also seems to be a link between phytochemicals and the Ah receptor. If phytochemicals are able to activate the receptor, this would be a clear indication that there is a link between the molecular mechanisms and the positive effect of broccoli and other vegetable compounds on human health. The researchers assume that the phytochemicals stimulate the maturation of LTi cells in the intestinal follicles by interacting with the Ah receptor, thereby fortifying the barrier function of the intestinal wall.Diefenbach and his team are carrying out feeding experiments with mice with the objective of studying the effect of different phytochemical concentrations on the role of the intestinal wall in fending off bacterial intruders and on the immunological reactions involving intestinal follicles. In future, the researchers will analyse the molecular effects of phytochemicals in order to obtain detailed insights into how phytochemicals fortify the intestinal immune barrier through their effect on LTi cells. “We also plan to screen compound databases to identify compounds that have the potential to be used for the prevention and treatment of chronic intestinal inflammatory diseases caused by bacteria,” Diefenbach said. However, clinical application is still a distant goal. On the other hand, a well-balanced vegetable-based diet can already be recommended for its many proven health benefits.
Further information:Prof. Dr. med. Andreas DiefenbachInstitute of Medical Microbiology and Hygiene University of Freiburg Tel.: +49 (0)761/ 203 - 65 22 Fax: +49 (0)761/ 203 - 66 51E-mail: andreas.diefenbach(at)uniklinik-freiburg.de