肝脏含有免疫细胞，可以摧毁乙型肝炎病毒感染的细胞，但不活跃。

In chronic hepatitis B, the liver contains immune cells that could destroy hepatitis B virus-infected cells but are inactive.

来自慕尼黑工业大学(TUM)的一个研究小组发现，肝脏血管中的细胞会启动一个“睡眠计时器”，关闭免疫细胞。

A team from the Technical University of Munich (TUM) has discovered that cells in blood vessels in the liver start a “sleep timer” that switches off immune cells.

据世界卫生组织(世卫组织)估计，全世界有2.5亿人患有慢性乙型肝炎。慢性乙型肝炎最常见的健康后果是肝损伤。

According to estimates by the World Health Organization (WHO), 250 million people worldwide suffer from chronic hepatitis B. The most common health consequence of chronic hepatitis B is liver damage.

通常，是身体对感染细胞的免疫反应导致了损害，而不是病毒本身:免疫细胞引发炎症过程，导致肝组织纤维化和肝癌。

Often, the body's immune response against infected cells causes the damage, not the virus itself: Immune cells trigger inflammatory processes that can lead to fibrosis – scarring of the liver tissue – and liver cancer.

在慢性感染中，一些受体能够识别并摧毁乙型肝炎病毒的免疫细胞处于失活状态。

Notably, in chronic infections, some immune cells whose receptors could recognize and destroy the Hepatitis B virus, are inactive.

由Knolle教授领导的团队在《自然》杂志上描述了这一现象的原因。

A team led by Prof. Knolle describes the reason for this in "Nature".

肝细胞由内衬内皮细胞的小血管提供。

They are supplied by small blood vessels that are lined with endothelial cells.

通过血液进入肝脏的免疫细胞只能通过这些内皮细胞的特殊开口到达被感染的肝细胞。

Immune cells that enter the liver via the blood only reach infected hepatocytes through special openings in these endothelial cells.

它们通过这些开口伸出延伸物到达被感染的肝细胞并破坏他们。

They protrude extensions through these openings to reach the infected hepatocytes and trigger their destruction.

在这样做的过程中，它们与内皮细胞密切接触。

In doing so, they are forced into close contact with the endothelial cells.

内皮细胞使用cAMP-PKA通路关闭受体的信号传递，而T细胞必须通过受体识别乙型肝炎病毒，并通过受体被激活。

Specifically, the endothelial cells use the cAMP-PKA pathway to switch off the signal transmission of the receptors with which the T cells recognize the Hepatitis B virus and through which they are activated.

结果，免疫细胞不再攻击被感染的细胞，最重要的是，免疫细胞无法增殖。

As a result, the immune cells no longer attack the infected cells and, above all, are unable to proliferate.

“我们认为这种机制的进化是为了保护肝脏，”Percy Knolle说。

"We think that this mechanism evolved to protect the liver," says Percy Knolle.

研究人员为此设计靶向免疫疗法，使T细胞不再接受内皮细胞的信号。

On the one hand, targeted immunotherapies are conceivable in which T cells are manipulated in such a way that they are no longer receptive to the signals from the endothelial cells.

另一方面，通过靶向这种机制的小分子来关闭这种机制。

On the other hand, it may also be possible to switch off the mechanism by small molecules targeting this mechanism.

科学家认为，这种疗法可以增强疫苗接种的效果，从而有助于对抗慢性乙型肝炎。

The researchers believe that such therapies could enhance the effect of vaccinations and thus help to combat chronic hepatitis B.

ORIGINAL PUBLICATION

Miriam Bosch, Nina Kallin, Sainitin Donakonda, Jitao David Zhang, Hannah Wintersteller, Silke Hegenbarth, Kathrin Heim, Carlos Ramirez, Anna Fürst, Elias Isaac Lattouf, Martin Feuerherd, Sutirtha Chattopadhyay, ... Dietmar Zehn, Dirk Wohlleber, Georg M. Lauer, Maike Hofmann, Souphalone Luangsay, Percy A. Knolle; "A liver immune rheostat regulates CD8 T cell immunity in chronic HBV infection"; Nature, 2024-7-10