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Article Dans Une Revue Hepatology (Baltimore, Md.) Année : 2019

Ductular reaction cells display an inflammatory profile and recruit neutrophils in alcoholic hepatitis.

Beatriz Aguilar-Bravo
  • Fonction : Auteur
Daniel Rodrigo-Torres
  • Fonction : Auteur
Silvia Arino
  • Fonction : Auteur
Mar Coll
  • Fonction : Auteur
Elisa Pose
  • Fonction : Auteur
Delia Blaya
  • Fonction : Auteur
Isabel Graupera
  • Fonction : Auteur
Luis Perea
  • Fonction : Auteur
Julia Vallverdu
  • Fonction : Auteur
Teresa Rubio-Tomas
  • Fonction : Auteur
Carolina Armengol
  • Fonction : Auteur
Antonio Lo Nigro
  • Fonction : Auteur
Peter Starkel
  • Fonction : Auteur
Ramon Bataller
  • Fonction : Auteur
Joan Caballeria
  • Fonction : Auteur
Juan Jose Lozano
  • Fonction : Auteur
Pere Gines
  • Fonction : Auteur
Pau Sancho-Bru
  • Fonction : Auteur

Résumé

Chronic liver diseases are characterized by the expansion of ductular reaction (DR) cells and the expression of liver progenitor cell (LPC) markers. In alcoholic hepatitis (AH), the degree of DR expansion correlates with disease progression and short-term survival. However, little is known about the biological properties of DR cells, their impact on the pathogenesis of human liver disease, and their contribution to tissue repair. In this study, we have evaluated the transcriptomic profile of DR cells by laser capture microdissection in patients with AH and assessed its association with disease progression. The transcriptome analysis of cytokeratin 7-positive (KRT7 ) DR cells uncovered intrinsic gene pathways expressed in DR and genes associated with alcoholic liver disease progression. Importantly, DR presented a proinflammatory profile with expression of neutrophil recruiting C-X-C motif chemokine ligand (CXC) and C-C motif chemokine ligand chemokines. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators such as CXCL5. Histologically, DR was associated with neutrophil infiltration at the periportal area. In order to model the DR and to assess its functional role, we generated LPC organoids derived from patients with cirrhosis. Liver organoids mimicked the transcriptomic and proinflammatory profile of DR cells. Conditioned medium from organoids induced neutrophil migration and enhanced cytokine expression in neutrophils. Likewise, neutrophils promoted the proinflammatory profile and the expression of chemokines of liver organoids. Conclusion: Transcriptomic and functional analysis of KRT7 cells indicate that DR has a proinflammatory profile and promote neutrophil recruitment. These results indicate that DR may be involved in the liver inflammatory response in AH, and suggest that therapeutic strategies targeting DR cells may be useful to mitigate the inflammatory cell recruitment in AH.
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Dates et versions

hal-04441691 , version 1 (19-03-2024)

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Beatriz Aguilar-Bravo, Daniel Rodrigo-Torres, Silvia Arino, Mar Coll, Elisa Pose, et al.. Ductular reaction cells display an inflammatory profile and recruit neutrophils in alcoholic hepatitis.. Hepatology (Baltimore, Md.), 2019, Hepatology (Baltimore, Md.), 69, pp.2180-2195. ⟨10.1002/hep.30472⟩. ⟨hal-04441691⟩

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