Functional modification of CD11c+ liver dendritic cells during liver regeneration after partial hepatectomy in mice.
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-gamma 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-gamma 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.
Department of Emergency and Organ Transplantation, Section of Gastroenterology and Endoscopy, University of Bari, Italy.
Antonino
A
Castellaneta
Alfredo
A
Di Leo
Ruggiero
R
Francavilla
Marcella
M
Margiotta
Michele
M
Barone
Annacinzia
A
Amoruso
Laura
L
Troiani
Angus W
AW
Thomson
Antonio
A
Francavilla
D000818:Animals; D001769:Blood; D039521:CD11c Antigen / Q000032:analysis*; D002452:Cell Count; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D015536:Down-Regulation; D004958:Estradiol / Q000097:blood; D015870:Gene Expression; D006498:Hepatectomy / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011960:Receptors, Estrogen / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
D039521:CD11c Antigen; D008024:Ligands; D011960:Receptors, Estrogen; D016753:Interleukin-10; D004958:Estradiol; D007371:Interferon-gamma; D051941:fms-Like Tyrosine Kinase 3