Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming.
Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming.
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能够逆转肝细胞启动所致T细胞功能障碍的Kupffer细胞亚群的鉴定
DOI：
10.1016/j.immuni.2021.05.005
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发表时间：
2021-09-14
期刊：
影响因子：
32.4
通讯作者：
Iannacone M
中科院分区：
文献类型：
--
作者：
De Simone G;Andreata F;Bleriot C;Fumagalli V;Laura C;Garcia-Manteiga JM;Di Lucia P;Gilotto S;Ficht X;De Ponti FF;Bono EB;Giustini L;Ambrosi G;Mainetti M;Zordan P;Bénéchet AP;Ravà M;Chakarov S;Moalli F;Bajenoff M;Guidotti LG;Ginhoux F;Iannacone M
Kupffer细胞(KCs)是一种高度丰富的、血管内、驻留在肝脏的巨噬细胞，以其清除和吞噬功能而闻名。KCS还可以向CD8+T细胞递呈抗原，促进耐受或效应器分化，但这些不同结果背后的机制尚不清楚。在这里，我们使用了乙肝病毒(HBV)感染的小鼠模型，在该模型中，识别肝细胞抗原的HBV特异性初始CD8+T细胞被驱动进入免疫功能障碍状态，以识别在白介素2(IL-2)注射时交叉递送肝细胞抗原的KCs(称为Kc2)亚群，从而改善T细胞的抗病毒功能。从包括Kc2在内的所有KCs中去除MHC-I，或选择性地耗尽Kc2，都会削弱IL-2逆转肝内预充引起的T细胞功能障碍的能力。综上所述，Kc2通过感知IL-2和交叉提呈肝细胞抗原，克服了肝脏微环境的耐受性潜力，为提高肝脏T细胞免疫提出了新的策略。KCs是IL-2在体内激活肝内免疫的T细胞所必需的，KCs对IL-2的反应和交叉存在的肝细胞AGS单细胞RNA-SEQ鉴定了两种不同的KCs群体，KC2具有丰富的IL-2传感机制和抗原提呈能力de Simone等人。描述了肝细胞启动的乙肝病毒特异性CD8+T细胞在给予IL-2后获得抗病毒效应功能的机制。这些机制依赖于KC，特别是迄今未被识别的KC亚群，称为KC2，它准备对IL-2和交叉存在的病毒抗原产生反应。
Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity. KCs are required for in vivo reinvigoration of intrahepatically primed T cells by IL-2 KCs respond to IL-2 and cross-present hepatocellular Ags Single-cell RNA-seq identifies two distinct populations of KCs KC2s have enriched IL-2 sensing machinery and Ag presentation capacity De Simone et al. delineate the mechanisms by which hepatocellularly primed HBV-specific CD8+ T cells acquire antiviral effector functions following IL-2 administration. These mechanisms rely on KCs and, in particular, on a hitherto unidentified KC subset, referred to as KC2, that is poised to respond to IL-2 and cross-present viral antigens.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
DOI：
10.1084/jem.20200298
发表时间：
2020-11-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fumagalli V;Di Lucia P;Venzin V;Bono EB;Jordan R;Frey CR;Delaney W;Chisari FV;Guidotti LG;Iannacone M
通讯作者：
Iannacone M
影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
5.4
作者：
GUIDOTTI, LG;MATZKE, B;CHISARI, FV
通讯作者：
CHISARI, FV
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P