乙肝免疫病理学代谢调节由髓源抑制细胞

StephenW

Nature Medicine | Article


Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells

    Laura J Pallett,    Upkar S Gill,    Alberto Quaglia,    Linda V Sinclair,    Maria Jover-Cobos,    Anna Schurich,    Kasha P Singh,    Niclas Thomas,    Abhishek Das,    Antony Chen,    Giuseppe Fusai,    Antonio Bertoletti,    Doreen A Cantrell,    Patrick T Kennedy,    Nathan A Davies,    Muzlifah Haniffa    & Mala K Maini   

   
    Nature Medicine    21,    591–600    (2015)  doi:10.1038/nm.3856

Received
    14 January 2015
Accepted
    31 March 2015
Published online
    11 May 2015



Infection with hepatitis B virus (HBV) results in disparate degrees of tissue injury: the virus can either replicate without pathological consequences or trigger immune-mediated necroinflammatory liver damage. We investigated the potential for myeloid-derived suppressor cells (MDSCs) to suppress T cell–mediated immunopathology in this setting. Granulocytic MDSCs (gMDSCs) expanded transiently in acute resolving HBV, decreasing in frequency prior to peak hepatic injury. In persistent infection, arginase-expressing gMDSCs (and circulating arginase) increased most in disease phases characterized by HBV replication without immunopathology, whilst L-arginine decreased. gMDSCs expressed liver-homing chemokine receptors and accumulated in the liver, their expansion supported by hepatic stellate cells. We provide in vitro and ex vivo evidence that gMDSCs potently inhibited T cells in a partially arginase-dependent manner. L-arginine–deprived T cells upregulated system L amino acid transporters to increase uptake of essential nutrients and attempt metabolic reprogramming. These data demonstrate the capacity of expanded arginase-expressing gMDSCs to regulate liver immunopathology in HBV infection.

StephenW

自然医学|文章


乙肝免疫病理学代谢调节由髓源抑制细胞

    劳拉ĴPallett，Upkar鳃，阿尔贝托Quaglia，琳达V辛克莱，玛丽亚JOVER - 科沃斯，安娜Schurich，卡莎P·辛格，尼克拉斯·托马斯，阿布舍克达斯，安东尼陈，朱Fusai，安东尼BERTOLETTI，多琳一个坎特雷尔，帕特里克·肯尼迪牛逼，弥敦道一戴维斯，Muzlifah Haniffa＆马拉ķ马伊尼

   
    自然医学21，591-600（2015）DOI：10.1038 / nm.3856

收到
    2015年1月14日
接受
    2015年3月31日
网上公布
    2015年5月11日



感染乙型肝炎病毒（HBV）的结果在不同程度的组织损伤：病毒可以复制无病理后果或引发免疫介导的坏死性炎症的肝脏损害。我们研究了髓源抑制细胞（肌源性干细胞）的电位以抑制在此设置的T细胞介导的​​免疫病理学。粒细胞肌源性干细胞（gMDSCs）急性HBV解决瞬时扩大，在减少频率之前达到峰值肝损伤。在持续感染，精氨酸酶表达gMDSCs（和精氨酸酶的循环）增加最多的特点是病毒复制疾病阶段没有免疫病理学，而L-精氨酸下降。 gMDSCs表达肝归巢趋化因子受体和在肝脏中积聚，其扩大通过肝星状细胞的支持。我们提供在体外和离体的证据表明，gMDSCs有效抑制T细胞中的局部精氨酸酶依赖性。 L-精氨酸剥夺T细胞上调系统l氨基酸转运增加必需的营养物质的吸收和代谢尝试重新编程。这些数据表明扩大精氨酸酶表达gMDSCs来调节在HBV感染肝脏免疫病理的能力。

StephenW

Regulation of immunopathology in hepatitis B virus infection

    Silvia Piconese        & Vincenzo Barnaba       

  

In the liver there is a fine balance between immune surveillance of blood-borne infections and regulation of immunopathology. A new study identifies a role for granulocytic myeloid-derived suppressor cells in limiting T cell–mediated immunopathology in hepatitis B virus infection.

免疫病理的乙肝病毒感染管制

    西尔维娅Piconese与文森佐BARNABA

  

在肝脏有血源性感染的免疫监视和免疫病理学的管制之间的平衡。一项新的研究确定了粒髓源抑制细胞限制T细胞介导的免疫病理乙肝病毒感染的作用。

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