Details

Autor(en) / Beteiligte

• Yissachar, Nissan
• Zhou, Yan
• Ung, Lloyd
• Lai, Nicole Y.
• Mohan, James F.
• Ehrlicher, Allen
• Weitz, David A.
• Kasper, Dennis L.
• Chiu, Isaac M.
• Mathis, Diane
• Benoist, Christophe

Titel

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

Ist Teil von

• Cell, 2017-03, Vol.168 (6), p.1135-1148.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •A novel organ culture system for the mouse intestine•Rapid modulation of neuronal gene expression by Th17/RORg+ Treg-inducing microbes•Differential direct activation of neurons by immune-modulating microbes•The nervous system influences the microbiome/immune system crosstalk A 3D organ culture system preserves the intestine architecture and allows modeling the interactions between intestinal cells, the immune system, microbes, and nutrients.