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INNATE IMMUNITY

Bile duct tuft cells regulate immune defences

Nature Reviews Immunology volume 22, page 273 (2022)Cite this article

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The gallbladder and extrahepatic bile ducts regulate the excretion of bile produced by the liver into the small intestine after feeding, which is required for the digestion of lipids. The biliary tree is thus exposed to the intestinal microbiota and requires antimicrobial defences, but despite inflammation of the bile ducts being a common cause of human pathology, we know little about how these immune responses are regulated. Rare chemosensory epithelial cells known as tuft cells — which have been described in the small intestine and airways — are also found in the gallbladder and bile ducts. Two papers in Science Immunology describe a role for biliary tuft cells in innate immune responses to intestinal bacteria.

Tuft cells in the airways and intestines have been shown to function as sentinel cells, monitoring for microbial products and allergens. Thus, Keshavarz et al. hypothesized that biliary tuft cells might monitor the bile ducts for bacteria and their products ascending from the small intestine. They showed that the microbial metabolite propionate induces gallbladder contraction in a manner dependent on tuft cells and requiring the fatty acid receptor FFAR2 and the cation channel TRPM5, both of which are expressed by tuft cells. Propionate-mediated activation of gallbladder tuft cells through a FFAR2–TRPM5 signalling pathway resulted in CysLT production that was required for smooth muscle contraction. Propionate stimulation also induced mucin release in a manner requiring expression of TRPM5 and choline acetyltransferase by tuft cells.

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References

Original articles

  • Keshavarz, M. et al. Cysteinyl leukotrienes and acetylcholine are biliary tuft cell cotransmitters. Sci. Immunol. 7, eabf6734 (2022)

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  • O’Leary, C. E. et al. Bile-acid-sensitive tuft cells regulate biliary neutrophil influx. Sci. Immunol. 7, eabj1080 (2022)

    Article  Google Scholar 

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Kirsty Minton

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  1. Kirsty Minton
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Correspondence to Kirsty Minton.

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Minton, K. Bile duct tuft cells regulate immune defences. Nat Rev Immunol 22, 273 (2022). https://doi.org/10.1038/s41577-022-00712-5

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  • DOI: https://doi.org/10.1038/s41577-022-00712-5

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