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

被引:24
|
作者
Castellaneta, A
Di Leo, A
Francavilla, R
Margiotta, M
Barone, M
Amoruso, A
Troiani, L
Thomson, AW
Francavilla, A
机构
[1] Univ Bari, Sect Gastroenterol & Endoscopy, Dept Emergency & Organ Transplantat, I-70124 Bari, Italy
[2] Univ Bari, Dept Biomed Evolut Age, Inst Pediat, I-70124 Bari, Italy
[3] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA
[4] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA
关键词
D O I
10.1002/hep.21098
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
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页码:807 / 816
页数:10
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