The mechanism of the immune response of lymph node cells has been revealed.

The Institute for Basic Science (IBS, President Noh Do Young) Center for Vascular Research led by Koh Gou Young (a distinguished professor at KAIST) established that the Hippo signaling pathway, which determines the size of the body organs, is essential for the immune responses of a lymph node. It is expected to help understand the immune response of a lymph node to pathogens such as SARS, MERS, and new coronaviruses.

A lymph node is a kidney-shaped immune organ, 1-20 mm in diameter, distributed throughout the body, mainly in the armpits, groin, neck, chest, and stomach. When pathogens in and out of the body enter the lymph nodes, immune cells in the lymph nodes are activated and mount an immune response. For the immune response to function appropriately, it is crucial to properly operate the signaling pathway in the various cells that make up the lymph nodes.

Conventionally, the Hippo signaling pathway is known to inhibit the growth of body organs and determine their size by promoting cell division inhibition and death. The study found that the Hippo signaling pathway is essential for regulating lymph node immune responses. The Hippo signaling pathway is a fibroblastic reticular cell that forms the lymph node's internal structure. It is activated early in the fibroblastic reticular cell differentiation and deactivated later to mount the immune response appropriately.

▲ Relationship between the degree of hippo signaling pathway activation and fibroblastic reticular cells differentiation in lymph node (Image by: IBS)

After preparing 20 kinds of mouse models with modified Yap/Taz protein genes involved in the Hippo signaling pathway, the research team examined how the immune response was regulated according to the degree of Hippo signaling pathway activation and fibroblastic reticular cells differentiation in a lymph node.

First, when the Hippo signaling pathway was inactivated at the beginning of fibroblastic reticular cell differentiation, abnormal immune response, and weight loss were observed. It means that cell differentiation hadn't been done correctly. Fibroblastic reticular cells secrete cytokines during pathogen infection to activate immune cells and induce immune responses. If fibroblastic reticular cells become fat cells over cell differentiation, cytokines are not secreted, and immune responses can't occur. In addition, when fibroblastic reticular cells, which form the internal structure of lymph nodes, decrease, it is difficult to provide enough space for immune responses to pathogens.

After the differentiation of fibroblastic reticular cells, it was observed that the Hippo signaling pathway was activated, the lymph nodes became fibrosis, and the immune function was paralyzed at the end. When fibroblastic reticular cells secrete a substance that promotes fibrosis, the lymph nodes become hardens and difficult to perform the immune function. Given that lymph node fibrosis occurs when the Yap/Taz protein is activated in the Hippo signaling pathway, Yap/Taz inhibitors are expected to be used for the treatment of fibrosis in organs.

The findings were published online in the international journal Nature Communications (IF 11.878) at 7:00 pm KST.

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