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Bile acid-sensitive tuft cells regulate biliary neutrophil influx.
O'Leary, Claire E; Sbierski-Kind, Julia; Kotas, Maya E; Wagner, Johanna C; Liang, Hong-Erh; Schroeder, Andrew W; de Tenorio, Jeshua C; von Moltke, Jakob; Ricardo-Gonzalez, Roberto R; Eckalbar, Walter L; Molofsky, Ari B; Schneider, Christoph; Locksley, Richard M.
Afiliación
  • O'Leary CE; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Sbierski-Kind J; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Kotas ME; Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Wagner JC; Department of Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Liang HE; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Schroeder AW; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • de Tenorio JC; Institute of Physiology, University of Zurich, Zurich, Switzerland.
  • von Moltke J; Department of Immunology, University of Washington, Seattle, WA, USA.
  • Ricardo-Gonzalez RR; Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
  • Eckalbar WL; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
  • Molofsky AB; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Schneider C; Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Locksley RM; Institute of Physiology, University of Zurich, Zurich, Switzerland.
Sci Immunol ; 7(69): eabj1080, 2022 03 04.
Article en En | MEDLINE | ID: mdl-35245089
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. Here, we show 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Biliar / Ácidos y Sales Biliares Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Sci Immunol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sistema Biliar / Ácidos y Sales Biliares Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Sci Immunol Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos