Immunoregulatory role of MΦ/DCs in the liver of murine malaria infected mice

MΦ/DCs 在鼠疟疾感染小鼠肝脏中的免疫调节作用

• 批准号: 16590343
• 负责人: WATANABE Hisami
• 金额: $ 2.24万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590343/
• 关键词: Murine malaria; NKT cells; Dendritic cells (DC); Myeloid DC; Plasmacytoid DC; Cytokine; Apoptosis inhibitor; Disease syndromes; 肝NKT細胞; マクロファージ; 原虫の早期排除; plasmocytoid DC; CD11c^<low> ClassII^-DC; parasitemia

We have already reported that one subset of NKT cells, known as CD3^<int>IL-2Rβ+NK1.1-subset, expanded in the liver of P.yoelli 17XNL-infected C57BL/6(B6) mice and contributed to protection against malaria. On the other hand, accumulating results of our studies suggested that liver dendritic cells (DCs) might play a critical role in the regulation of immune responses through activation of liver NKT cells after malarial infection. However, this approach has not been clearly elucidated. In this study we attempted to analyze the phenotype and function of liver DCs in malaria infected mice.DCs are classified into two majour subpopulations ; myeloid DC (mDC) and plasmacytoid DC (pDC). Murine liver had high absolute number of PDCA-1+CD11c^<low>I-A-B220+DC (pDC) which produced IFN-α by stimulation with CpG in vitro. PDCA-1-CD11c^<high>I-A+B220-DC (mDC) were dominant in the spleen. DCs of both phenotypes were able to produce IL-12, IL-10 and TNFα. CD11c^<low>I-A-DC isolated from malaria infect … More ed mice increased in the liver and spleen at acute phase (7 days). These cells showed high expression of CD86 but decreased PDCA-1 expression and IFN-α production. I-A-CD11c^<low>DCs isolated from infected mice showed impaired production of cytokines as compared with mDCs. PDCA-1^+ cells in CD11c^<low>I-A- fraction of liver and spleen reappeared at recovery phase (after 25 days) of malarial infection. These results indicate that while mDCs activate NKT cells via cytokines and that activated NKT cells promote the protective activity and disease syndromes in malaria infected mice. pDCs induce the immunosuppressive effects due to impaired production of IFN-α. AIM (apoptosis inhibitor expressed by MΦ) deficient mice lack some of MΦ and DC functions and were found to recover more quickly from malarial infection than B6 mice. γδT cells expanded in the liver and spleen, especially in the recovery phase. These findings clearly showed the phenotypical and functional change of DCs in the liver and may support the view that liver DC regulate the function of NKT cells in the liver after malarial infection. Less

我们已经报道了NKT细胞的一个亚群，称为CD3^<int b> IL-2Rβ+ nk1.1亚群，在p.j oelli 17xnl感染的C57BL/6（B6）小鼠的肝脏中扩增，并有助于抵抗疟疾。另一方面，我们越来越多的研究结果表明，肝脏树突状细胞（dc）可能通过激活肝脏NKT细胞在疟疾感染后的免疫应答调节中发挥关键作用。然而，这种方法还没有得到明确的阐明。在本研究中，我们试图分析疟疾感染小鼠肝脏dc的表型和功能。dc被分为两个主要亚群；髓样DC （mDC）和浆细胞样DC （pDC）。体外CpG刺激小鼠肝脏产生IFN-α的PDCA-1+CD11c^绝对数量高< >I-A-B220+DC （pDC）绝对数量低。脾脏以PDCA-1-CD11c^<高>I-A+B220-DC （mDC）为主。两种表型的dc均能产生IL-12、IL-10和TNFα。急性期（7天）小鼠肝脏和脾脏中CD11c^<低>I-A-DC增多。这些细胞显示CD86的高表达，但PDCA-1的表达和IFN-α的产生降低。与mdc相比，从感染小鼠中分离的I-A-CD11c^<低> dc显示细胞因子的产生受损。在疟疾感染恢复期（25天后），肝脏和脾脏CD11c^<低>I-A-部分的PDCA-1^+细胞再次出现。这些结果表明，mDCs通过细胞因子激活NKT细胞，激活的NKT细胞促进疟疾感染小鼠的保护活性和疾病综合征。pDCs通过抑制IFN-α的产生而诱导免疫抑制作用。AIM （MΦ表达的凋亡抑制剂）缺陷小鼠缺乏MΦ和DC的部分功能，并且发现比B6小鼠从疟疾感染中恢复得更快。肝脏和脾脏中γδT细胞扩增，在恢复期尤甚。这些发现清楚地显示了肝脏DC的表型和功能变化，并可能支持疟疾感染后肝脏DC调节肝脏NKT细胞功能的观点。少

项目成果

Wall shear stress and intrahepatic leukocytes of graft in living related donor liver transplantation

活体肝移植移植物壁切应力和肝内白细胞

• 发表时间: 2004
• 期刊: Hepatogastroenterology 51(56)
• 作者: Sato Y;Watanabe H;Hatakeyama K
• 通讯作者: Hatakeyama K

Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe concanavalin A-induced hepatitis

• DOI: 10.4049/jimmunol.173.1.579
• 发表时间: 2004-07-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Saito, T;Okumura, A;Yamagoe, S
• 通讯作者: Yamagoe, S

Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites.

由于抑制肝脏和其他部位的红细胞生成，抗红细胞生成素抗体可预防疟疾。

• 发表时间: 2005
• 期刊: Immunology and Cell Biology 83
• 作者: Tsubata;S.
• 通讯作者: S.

Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ gammadelta T cells with double-negative CD4- CD8- phenotype in the liver.

• 发表时间: 2006
• 期刊: Immunology
• 影响因子: 6.4
• 作者: H. Bakir;C. Tomiyama-Miyaji;Hisami Watanabe;T. Nagura;T. Kawamura;H. Sekikawa;T. Abo

Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially NKT cells, double-positive CD4^+8^+ cells and B220^+T cells, in mice.

小鼠肠道淋巴细胞亚群的比例和数量存在年龄依赖性变化，特别是NKT细胞、双阳性CD4^8细胞和B220^T细胞。

• 发表时间: 2004
• 期刊: Immunology 113
• 作者: Ishimoto;Y.
• 通讯作者: Y.