An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk

Citation:

Yissachar, N. ; Zhou, Y. ; Ung, L. ; Lai, N. Y. ; Mohan, J. F. ; Ehrlicher, A. ; Weitz, D. A. ; Kasper, D. L. ; Chiu, I. M. ; Mathis, D. ; et al. An Intestinal Organ Culture System Uncovers a Role for the Nervous System in Microbe-Immune Crosstalk. Cell 2017, 168, 1135–1148. Copy at http://www.tinyurl.com/y5rrhycg
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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.

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Last updated on 11/09/2020