@article {yissachar2017intestinal, title = {An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk}, journal = {Cell}, volume = {168}, number = {6}, year = {2017}, pages = {1135{\textendash}1148}, publisher = {Cell Press}, abstract = { Investigation of host-environment interactions in the gut would benefit from a culture system that maintained tissue architecture yet\ allowed tight experimental control. We devised a microfabricated organ culture system that viably preserves the normal multicellular composition of the mouse intestine, with luminal flow to control perturbations (e.g., microbes,\ drugs). It enables studying short-term responses of diverse gut components (immune, neuronal, etc.). We focused on the early response to bacteria that induce either Th17 or RORg+\ T-regulatory (Treg) cells in\ vivo. Transcriptional responses partially reproduced in\ vivo signatures, but these microbes elicited diametrically opposite changes in expression of a neuronal-specific gene set, notably nociceptive neuropeptides.\ We demonstrated activation of sensory neurons\ by microbes, correlating with RORg+\ Treg induction. Colonic RORg+\ Treg frequencies increased in mice lacking TAC1\ neuropeptide precursor and decreased in capsaicin-diet fed mice. Thus, differential engagement of the enteric nervous system\ may partake in bifurcating pro- or anti-inflammatory responses to microbes. }, url = {https://www.sciencedirect.com/science/article/pii/S0092867417301873?via\%3Dihub}, author = {Yissachar, Nissan and Zhou, Yan and Ung, Lloyd and Lai, Nicole Y and Mohan, James F and Ehrlicher, Allen and Weitz, David A and Kasper, Dennis L and Chiu, Isaac M and Mathis, Diane and others} }