Claire E. O’Leary, Ph.D. (HHMI - UCSF) Faculty Search Candidate Webinar Only

Claire E. O’Leary, Ph.D. (HHMI - UCSF) Faculty Search Candidate Webinar Only

Butler Seminar Series

Event Date/Location

January 26, 2022 - 12:00 pm to 1:00 pm

Speaker

  • Claire E. O’Leary

    Postdoctoral Research Scholar
    Howard Hughes Medical Institute
    UCSF School of Medicine

Topic

Foul Humors: Bile acids, tuft cells and inflammatory control in digestive tissues

Inflammation and dysfunction of the extrahepatic biliary tree are common causes of human pathology, including gallstones and cholangiocarcinoma. Despite this, we know little about the local regulation of biliary inflammation. Tuft cells, rare sensory epithelial cells, are particularly prevalent in the mucosa of the gallbladder and extrahepatic bile ducts. We found that biliary tuft cells express a core genetic tuft cell program in addition to a tissue-specific gene signature, and, in contrast to small intestinal tuft cells, decreased postnatally, coincident with maturation of bile acid production. Manipulation of enterohepatic bile acid recirculation revealed that tuft cell abundance is negatively regulated by bile acids, including in a model of obstructive cholestasis in which inflammatory infiltration of the biliary tree correlated with loss of tuft cells. Unexpectedly, tuft cell-deficient mice spontaneously displayed an increased gallbladder epithelial inflammatory gene signature accompanied by neutrophil infiltration that was modulated by the microbiome. We propose that biliary tuft cells function as bile-acid sensitive negative regulators of inflammation in biliary tissues, and serve to limit inflammation under homeostatic conditions.

 

Audience

Webinar Only

Host

Alex Ploss, Molecular Biology Dept.