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 ofDCin liver regeneration. After 75% partial hepatectomy (PH) inmale 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%PHin 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
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