Liver Sinusoidal Endothelial Cells Contribute to Hepatic Antigen-Presenting Cell Function and Th17 Expansion in Cirrhosis
Por:
Caparros, E, Juanola, O, Gomez-Hurtado, I, Puig-Kroger, A, Pinero, P, Zapater, P, Linares, R, Tarin, F, Martinez-Lopez, S, Gracia-Sancho, J, Gonzalez-Navajas, J and Frances, R
Publicada:
1 may 2020
Ahead of Print:
15 may 2020
Resumen:
Hepatic immune function is compromised during cirrhosis. This study investigated the immune features of liver sinusoidal endothelial cells (LSECs) in two experimental models of cirrhosis. Dendritic cells, hepatic macrophages, and LSECs were isolated from carbon tetrachloride and bile duct-ligated rats. Gene expression of innate receptors, bacterial internalization, co-stimulatory molecules induction, and CD4+ T cell activation and differentiation were evaluated. Induced bacterial peritonitis and norfloxacin protocols on cirrhotic rats were also carried out. LSECs demonstrated an active immunosurveillance profile, as shown by transcriptional modulation of different scavenger and cell-adhesion genes, and their contribution to bacterial internalization. LSECs significantly increased their expression of CD40 and CD80 and stimulated CD4+ T cell activation marker CD71 in both models. The pro-inflammatory Th17 subset was expanded in CCl4-derived LSECs co-cultures. In the bile duct ligation (BDL) model, CD4+ T cell differentiation only occurred under induced bacterial peritonitis conditions. Differentiated pro-inflammatory Th cells by LSECs in both experimental models were significantly reduced with norfloxacin treatment, whereas Foxp3 tolerogenic Th CD4+ cells were expanded. Conclusion: LSECs' participation in the innate-adaptive immune progression, their ability to stimulate pro-inflammatory CD4+ T cells expansion during liver damage, and their target role in norfloxacin-induced immunomodulation granted a specific competence to this cell population in cirrhosis.
Filiaciones:
:
Univ Miguel Hernandez, Dept Med Clin, Alacant 03550, Spain
:
Univ Miguel Hernandez, Dept Med Clin, Alacant 03550, Spain
Gomez-Hurtado, I:
Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain
Puig-Kroger, A:
Hosp Gen Univ Gregorio Maranon, Inst Invest Sanitaria Gregorio Maranon IiSGM, Madrid 28007, Spain
:
Hosp Gen Univ Alicante, Inst ISABIAL, Alicante 03010, Spain
:
Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain
Hosp Gen Univ Alicante, Inst ISABIAL, Alicante 03010, Spain
Univ Miguel Hernandez, Dept Farmacol, Alacant 03550, Spain
:
Univ Miguel Hernandez, Dept Med Clin, Alacant 03550, Spain
:
Hosp Gen Univ Alicante, Inst ISABIAL, Alicante 03010, Spain
:
Univ Miguel Hernandez, Dept Med Clin, Alacant 03550, Spain
Gracia-Sancho, J:
Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain
Inst Invest Biomed August Pi i Sunyer IDIBAPS, Barcelona 08036, Spain
:
Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain
Hosp Gen Univ Alicante, Inst ISABIAL, Alicante 03010, Spain
Univ Miguel Hernandez, Dept Farmacol, Alacant 03550, Spain
:
Univ Miguel Hernandez, Dept Med Clin, Alacant 03550, Spain
Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain
Hosp Gen Univ Alicante, Inst ISABIAL, Alicante 03010, Spain
Gold, Green Published
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