uni'wissen 02-2012 ENG

immune system, identify “enemies.” The more well-known adaptive immune system doesn’t learn how to distinguish the body’s own bacteria from foreign bacteria until after birth. Through contact with the outside world, countless specif- ic antigen receptors develop in the course of time which T cells in the adaptive immune sys- tem can use to identify potential invaders. The LTi cells do not have such detection receptors at their disposal. “However, we know more about how they fend off pathogens,” says Diefenbach. LTi cells produce soluble factors, including inter- leukin 22 (IL-22), which causes the cells of the intestinal epithelium to form proteins that can be used to combat germs. T cells also release IL-22. In their case, the aryl hydrocarbon receptor (AhR) boosts the production of the factor. Infants are provided with glucosinolates through mother’s milk. The Freiburg researchers suspect that these plant chemicals influence the development of the innate immune system in the intestines in mice as well as in humans. Photo: Molin/Fotolia LTi cells also have the AhR. What role does it play in them? In order to find the answer to this question, Diefenbach’s PhD candidate Elina Kiss from the Spemann Graduate School of Biology and Medicine (SGBM) of the University of Freiburg switched off the receptor in her mice: The level of IL-22 decreased, and there was a hundredfold drop in the amount of LTi cells. “We didn’t see any more patches and follicles under the microscope,” says Kiss. Hence, the aryl hy- drocarbon receptor is crucial. But what sub- stances stimulate the receptor in LTi cells? Dioxin, the most well-known binding partner of the AhR, is toxic and thus does not come into consideration. “Since we are working on the di- gestive tract, nutrients struck us as the most in- teresting candidates,” explains Kiss. A review of the literature led to the discovery that the aryl hydrocarbon receptor has a binding site for plant substances that glucosinolates can dock onto. Kiss could not simply feed her mice these sub- stances exclusively, because they would not have survived it in the long run. The solution was a mouse diet: Kiss gave half of her animals food in which the glucosinolates had been industrially removed but which contained all other essential nutrients. These mice ended up looking like those without the AhR – they had very few LTi cells, hardly any IL-22, no follicles. The mice that received glucosinolates, on the other hand, de- veloped in a completely normal way. “We were surprised to find out that the entire system is so dependent on AhR and glucosinolates,” says the Finn. When she came to Freiburg in 2008, she was familiar with molecular biological tech- niques, but she was new to immunological re- Various types of immune cells collect in the crypts, the indentations between two intestinal villi (red: LTi cells; blue: B cells) and form follicles. The follicles protect mice from infections and chronic- inflammatory diseases. 26

uni'wissen 02-2012 ENG

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