Functional modification of CD11c+ liver dendritic cells during liver regeneration after partial hepatectomy in mice

Authors

  • Antonino Castellaneta,

    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
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    • Antonino Castellaneta and Alfredo Di Leo contributed equally to this work and should be considered co-first authors.

  • Alfredo Di Leo,

    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
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    • Antonino Castellaneta and Alfredo Di Leo contributed equally to this work and should be considered co-first authors.

  • Ruggiero Francavilla,

    1. Department of Biomedicine of Evolutive Age, Institute of Pediatrics, University of Bari, Italy
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  • Marcella Margiotta,

    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
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  • Michele Barone,

    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
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  • Annacinzia Amoruso,

    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
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  • Laura Troiani,

    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
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  • Angus W. Thomson,

    1. Departments of Surgery and Immunology, University of Pittsburgh, Pittsburgh, PA
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  • Antonio Francavilla

    Corresponding author
    1. Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy
    • Department of Emergency and Organ Transplantation, Section of Gastroenterology, University of Bari, Padiglione Chini (4th floor), P.zza Giulio Cesare,11, 70124 Bari, Italy
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    • fax: (39)-080-5593251


  • Potential conflict of interest: Nothing to report.

Abstract

Local immunosuppression within the liver and sex steroid changes, in both blood and tissue during liver regeneration, are well-recognized events. Dendritic cells (DC) play pivotal roles in the induction and regulation of immune responses. Their numbers are expanded markedly in vivo by fms-like tyrosine kinase 3 ligand (Flt3L) administration, without modification of their maturation state. Recent evidence suggests that estrogen can modulate DC function and promote a Th2-type immune response. Few data are available concerning the role of DC in liver regeneration. After 75% partial hepatectomy (PH) in male C57BL/6 mice, CD11c+ liver (L)DC increased significantly within 6 hours and maintained an immature phenotype. Numbers returned to pre-hepatectomy levels by 24 hours. The expanded LDC population showed increased IL-10 and reduced IFN-γ gene transcription. Using these DC compared with control LDC as T cell stimulators in 72-hour mixed leukocyte cultures, IL-10 production was enhanced and IFN-γ production reduced. LDC isolated 6 hours after 75% PH exhibited enhanced estrogen receptor (ER) expression, concomitant with increased serum estrogen levels. By contrast, spleen (S)DC isolated before and after PH showed no significant changes in their function (maturation state, T cell stimulatory activity, cytokine production, and ER expression). Increased liver regeneration (more than 50%) was observed 48 hours after 40% PH in the Flt3L-pretreated compared with the PBS group. In conclusion, interstitial LDC may play a key role in local immune regulation during liver regeneration, possibly linking estrogen-mediated immune modulation and hepatocyte proliferation. (HEPATOLOGY 2006;43:807–816.)

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