Reinhold Förster: Tracker of the immune system

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At the Hannover Medical School, Reinhold Förster is studying how immune cells migrate to the lymph nodes. Source: MHH/Kaiser

31.12.2012  - 

Immune researcher Reinhold Förster was always fascinated by the lymph nodes: “They’re actually a solid organ, while the interior is highly mobile,” says the Director of the Institute of Immunology at the Hannover Medical School (MHH). Förster is exploring how the switching points of the immune system are organised, and how immune cells migrate to the lymph nodes. To shed some light on these mechanisms, he is employing the technique of two-photon laser microscopy. His findings recently garnered the 51-year-old the €2.5 million Advanced Grant from the European Research Council (ERC).

Lymph nodes play a vital role in the immune system. The defences against invading pathogens such as viruses, bacteria or fungi are initiated in these ‘filtering stations’. Moreover, they are important to ensure that the immune system is not directed against the body or against harmless substances from the environment – in the case of allergies, for example. Reinhold Förster is occupied with the question of why the immune cells migrate to the lymph nodes, and the role played by so-called chemokines and chemokine receptors. Chemokines are attractants that bring about a movement impulse in cells. Förster is regarded an international expert on the subject, and this November won the prestigious Advanced Grant from the ERC. At €2.5 million over a period of five years, the award is Europe's most prestigious individual grant for European researchers.

An interest sparked at the LMU

The path of the graduate veterinarian has been anything but predicable. The native Bavarian realised fairly early on that  “the competition among veterinarians is high, the hours are not regulated and there are few opportunities for interexchange with colleagues.” In addition, Förster found the practical application of his knowledge to be a sobering experience. “In the livestock area, animals are almost never treated individually. Either they’re all given antibiotics or the individual animal is slaughtered.” And so in 1991 the vet decided against operating his own practice and undertook a doctorate at the Ludwig-Maximilians University in Munich. “At this time, the world-famous virologist Anton Mayr was also active at the university. That was a chance to get my fingers into molecular biology, of which I had no idea at the time, of course,” says the immunologist today. He eventually landed in a working group headed by Martin Lipp, and worked with him on the so-called CXCR5 receptor. As it turned out, this chemokine receptor is largely responsible for the migration of immune cells to the lymph nodes. “This sparked something between me and the research,” says Förster. Indeed, the field resulted in some highly in-depth and laborious work from the fledgling scientist. “I often put in 80-hour weeks – but I didn’t find it so exhausting. It all served to help satisfy my curiosity.” A not unwelcome side effect was that his findings were internationally very well received. (cf. Cell 1996, Ed.87, pp.1037) “Our work is discussed in the immunology text books and has been cited thousands of times. That’s just great,” says the proud immune researcher. 

Gossamer-thin syringes developed for lymphatic vessels

Today, Förster is occupied with the question of to which extent a dysfunction of the lymphatic organs can be responsible for diseases. According to Förster, there are two fundamental means by which immune cells migrate to a lymph node. One is via highly specialised blood vessels known as HEV. “This path was very well understood even 20 years ago,” says the immunologist. The second path passes through a particular part of the so-called sclera, via the lymph vessels and onwards to the nodes. Once there, the immune cells must actively migrate into the node. “We know next to nothing about this process,” says Förster, who closely follows the paths of the immune cells like a ‘tracker in the African bush’. The problem here is the extremely tiny lymph vessels. To be able to track cells in the course of migration, they must first be marked and then injected into the veins. For a long time this approach was considered impossible; the lymph veins between some lymph nodes in mice are only about 50 microns in diameter. By comparison, a human hair measures about 75 microns across. To work on this scale, Försters’s team recently developed a unique micro-injection technology. “I had people here who set out to develop these microinjectors using glass. It did not take long until we were able to inject marked immune cells in the lymph vessels,” says Förster. Only after this step could the researchers observe immune cells in the course of migration in mice with a two-photon laser. 

A cross-section of a lymph node under the microscope: Normal dendritic cells (green) migrate into the interior, while specially marked cells (red) remain on the sidelines.Source: MHH

Vaccinating intestinal lymph nodes through the skin

Among other things, Förster and his team intend to use the findings to examine the scattering behaviour of tumours. He also hopes to improve the vaccines used to combat diarrhoeal diseases: “When you understand how the activation of cells in the intestinal lymph nodes differs from those in the skin lymph nodes, we can find out how to also vaccinate in the intestine via the skin lymph nodes.” The findings here could be of great importance – one third of all children in developing countries die of diarrhoeal diseases. For Förster – himself a father of three children –the funding for the ERC Advanced Grant couldn’t have come at a better time: “The award gives us visibility in Europe, but for me it’s the complete freedom to conduct research that interests me. It’s nice because you don’t have to bend to others’ wishes.”Some advice from the immunologist for those who might want to work in his field: “You should think carefully about which way you want to go, and then follow that with a passion. When you’re faced with a doctoral thesis, then this should take priority – and no trips around the world without a clear understanding of where to and why.” This is something that he knows from experience: “Become independent as soon as you can. Successfully leading my first working group helped tremendously here.” 

Author: Kolja Schümann