Role of galanin on immune cell migration and polarization

The project titled The role of the regulatory peptide galanin on immune cell migration and polarization investigates the communication and interaction between the nervous and immune systems. The exchange of these two systems is essential for a well-functioning organism to be able to adapt to an acute challenge of the body like an infection or a chronic inflammation but also acute or chronic stress. Diverse chemical messengers are responsible for the exchange of information and one group of these messengers are called regulatory peptides. These regulatory peptides are released by nerve cells but also by immune cells and bind to other immune cells to exchange information about the condition of the microenvironment. The regulatory peptide of our interest is named galanin, which can interact with three different surface proteins (also called receptors) of cells to transmit different signals. The involvement of galanin and its receptors in different inflammatory models including psoriasis and colitis has been proven. To date, it is unclear which immune cells mediate the pro- or anti-inflammatory functions of the galanin system during acute/chronic inflammation and homeostasis. Based on the scientific literature and our preliminary data, we hypothesize that galanin induces the production of signaling molecules in immune cells, which are needed to attract other immune cells to the area of inflammation. Furthermore, due to the fact that galanin plays a role in the later stages of inflammation, we hypothesize that galanin affects the activation and polarization of specific immune cells (T cells), which are part of the immune cell memory. In in vitro studies, we will first use primary human immune cells, which will be treated with galanin and the effect of this treatment on the ability to influence immune cell migration will be determined. Furthermore, in mice, which either lack galanin or its receptors in their body, differences in the immune response upon an acute inflammation will be analyzed and compared to the response in wild-type animals. Our studies will reveal which immune cells are a source and a target of galanin and how this systems affects the function of diverse immune cell subpopulations. The results of the study will provide a basis for preclinical studies aimed at the therapeutic application of galanin receptor ligands in certain inflammatory diseases. 1

The project "The role of galanin in immune cell migration and polarization" investigated how the nervous system and the immune system communicate and cooperate with each other through a small protein molecule of the galanin peptide family. The regulation of the immune system is crucial for the body's response to acute or chronic inflammation. Regulatory peptides, such as galanin, are important messenger substances, which are released by nerve cells and immune cells and regulate inflammation. Galanin acts via various receptors on cell surfaces and can therefore trigger different signals in cells. Which immune cells are regulated by galanin has not yet been sufficiently investigated. In earlier studies, our research group was able to show that certain immune cells have galanin receptors on their surface and that thereby galanin influences the activation of blood cells such as neutrophils, macrophages and monocytes. These cells are important components of the immune system and play a central role in fighting infections. In preliminary studies, we have also shown that galanin plays a role in various inflammatory diseases, such as psoriasis and intestinal inflammation. Therefore, we hypothesized that galanin and its receptors also play a role in inflammation of the abdominal cavity in the course of peritonitis and sepsis. Peritonitis is an inflammation of the peritoneum, and sepsis is a dangerous reaction of the body to an infection. Both can, if not treated in time, lead to a strong and sometimes excessive immune response, which is responsible for organ failure and possibly death of the patient. To determine the role of galanin and galanin receptors 2 and 3 in peritonitis and sepsis, chemically induced peritonitis and bacterial sepsis were induced in mice, respectively. For this purpose, we used genetically modified animals lacking galanin or galanin receptors (knockout mice). The course of the diseases in the knockout animals was compared with normal wild-type animals. Our results show that in the absence of galanin receptors 2 and 3 the migration of neutrophils was reduced and in turn the migration of macrophages in the abdominal cavity was increased. In addition, the production of signaling substances that recruit immune cells to sites of inflammation in the body to fight the infection were altered. The galanin system also influenced the activation of special immune cells (T cells), which are an important component of immunological memory. These findings form the basis for future studies on the development of therapeutics that reduce the massive immune response in severe inflammatory diseases. One promising possibility would be the use of substances that specifically modulate galanin receptors in order to control and mitigate the inflammatory response.