%0 Journal Article %J Cell %D 2017 %T An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk %A Yissachar, Nissan %A Zhou, Yan %A Ung, Lloyd %A Lai, Nicole Y %A Mohan, James F %A Ehrlicher, Allen %A Weitz, David A %A Kasper, Dennis L %A Chiu, Isaac M %A Mathis, Diane %A others %X

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.

%B Cell %I Cell Press %V 168 %P 1135–1148 %G eng %U https://www.sciencedirect.com/science/article/pii/S0092867417301873?via%3Dihub %N 6