Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance.
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DOI：
10.1371/journal.pone.0037202
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen CL
中科院分区：
文献类型：
--
作者：
Nakano T;Lai CY;Goto S;Hsu LW;Kawamoto S;Ono K;Chen KD;Lin CC;Chiu KW;Wang CC;Cheng YF;Chen CL
肥大细胞在肝移植排斥和耐受中的确切作用尚不清楚。本研究采用大鼠原位肝移植模型，探讨肥大细胞在免疫调节和肝再生诱导耐受中的作用。干细胞因子（SCF）及其受体c-Kit，这是至关重要的迁移和发展，不仅干细胞，而且肥大细胞，显着增加的耐受性肝脏相比，拒绝的肝脏。肥大细胞类胰蛋白酶，高亲和力IgE受体，组胺的显着升高，表明肥大细胞在奥尔特后的致耐受性阶段的肝移植物中的激活。共聚焦显微镜免疫组化分析清楚地显示肥大细胞、Foxp 3 + T细胞、γδ T细胞和肝源性肝祖细胞的共定位，并显示SCF、IL-9、IL-10、TGF-β1和IL-17在耐受性奥尔特模型的供体移植物中的高表达与免疫调节和肝再生相关。通过体外研究评估了肥大细胞和其他细胞之间的串扰，证明同基因骨髓来源的肥大细胞（BMMC）与幼稚脾细胞或原代肝细胞共培养，分别通过丝裂原刺激或肥大细胞脱粒显著增加脾γδ T细胞的数量，并显著诱导肝细胞增殖。我们的研究结果表明，肥大细胞在供体移植物中可能发挥重要作用，诱导/维持免疫耐受和肝再生，导致肝细胞从供体到受体的替代。
The precise roles of mast cells in liver allograft rejection and tolerance are still unknown. This study aimed to explore the roles of mast cells in immune regulation and liver regeneration for tolerance induction by using rat models of orthotopic liver transplantation (OLT). Stem cell factor (SCF) and its receptor c-Kit, which are critical to the migration and development of not only stem cells but also mast cells, significantly increased in the tolerogenic livers as compared with rejected livers. The significant elevation of mast cell tryptase, high-affinity IgE receptor, and histamine suggested the activation of mast cells in liver allografts at the tolerogenic phase after OLT. Immunohistochemical analysis using confocal microscope clearly showed colocalization of mast cells, Foxp3+ Tregs, γδ T cells, and recipient-derived hepatic progenitor cells with higher expression of SCF, IL-9, IL-10, TGF-β1, and IL-17 related to immunoregulation and liver regeneration in the donor grafts of a tolerogenic OLT model. Cross-talk among mast cells and other cells was evaluated by in vitro studies demonstrating that syngeneic bone marrow−derived mast cells (BMMCs) co-cultured with naïve splenocytes or primary hepatocytes significantly increased the population of splenic γδ T cells by mitogen stimulation or by mast cell degranulation, and also significantly induced the hepatocyte proliferation, respectively. Our results suggested that mast cells in the donor grafts may play important roles in the induction/maintenance of immune tolerance and liver regeneration resulting in the replacement of hepatic cells from donor to recipient.
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影响因子：
6.2
作者：
Koskinen, PK;Kovanen, PT;Lemström, KB
通讯作者：
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10.1152/ajpgi.00024.2008
发表时间：
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影响因子：
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作者：
Li, Jinzheng;Lai, Xing;Gong, Jianping
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Gong, Jianping