Division of Labor in the Immune System

16/11/2012
Professor Zenke immune system Copyright: Peter Winandy

Professor Dr. Martin Zenke (front), Dr. Thomas Hieronymus, and Dr. Kristin Seré from the RWTH Aachen Chair of Cellular Biology investigate the development of stem cells into immune cells. Their research aims at understanding the complex system of immune defense, for example in skin, and to open the perspective for the development of new vaccines.

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RWTH Aachen scientists have now found out how cells in the immune system work together and develop from stem cells

If a security guard spots an intruder with malicious intentions, he or she must get active. But who's watching out for further intruders in the meantime, while the guard is busy? And what about the life of a security guard on constant duty, if it is a sentinel cell?

These questions have now been addressed by scientists at RWTH Aachen University Hospital and the Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany. They found that sentinel cells in skin with a key function in immune defense are regenerated from stem cells in bone marrow. The current assumption was that every person is born equipped with these sentinel cells and these cells have to last for life.

It took the RWTH scientists almost five years to work out the origin of these sentinel cells and their results are now published in the high-profile journal IMMUNITY.

Immune mechanism deciphered

The sentinel cells in skin were discovered in 1868 by Paul Langerhans and are therefore called Langerhans cells. They exhibit branch-like extensions and were named dendritic cells - dendros is the Greek word for tree. Langerhans cells are located in the epidermis and have a very important job: The skin is the largest organ of the body, which is in permanent contact with the outside world and thus has a special function in immune defense. If bacteria, viruses or chemicals penetrate into skin, Langerhans cells capture them and transport them to the lymph nodes. There they "present" the invaders to specialized immune cells and trigger specific defense mechanisms. The role that dendritic cells play in the immune system is considered highly important – in 2011, the Nobel Prize in Medicine was awarded for their discovery and elucidation of function in adaptive immunity.

When Langerhans cells have left their positions within the skin they need to be replaced. Initially, scavenger cells called monocytes / macrophages migrate into the skin and also develop dendritic structures. Until now scientists assumed that these cells develop further into Langerhans cells. The Aachen scientists have now discovered that these monocyte / macrophage-derived cells are not long-lived and disappear with time. Therefore they cannot fully replace the Langerhans cells. The scientists showed that after one to two weeks new Langerhans cells were formed from stem cells in the bone marrow and the protective function of skin as an immune barrier was restored. Thus, sentinel cells in skin are much more dynamic than initially thought. This division of labor between Langerhans cells and monocytes / macrophages secures the immune barrier provided by the skin.

Many years of research for several lines of evidence

"Since our data challenge a long-standing dogma, we had to be particularly meticulous and confirm our hypotheses by several lines of evidence," explains Professor Martin Zenke. The Chair of Cell Biology heads the research group that cooperates on this topic with a Japanese team. They showed, for example, that in mice deficient for Langerhans cells, bone marrow transplantation allowed formation of new Langerhans cells.

The results reported represent studies in basic research. The regulation of skin immunity is very complex and involves many different immune cells and factors. For example, the role of Langerhans cells in autoimmune diseases of skin, such as psoriasis, is not yet fully understood. The results of the Aachen scientists provide new insights that could also be the foundation for the development of new vaccines.

Sabine Busse

Reference

Seré, K., Baek, J.-H., Ober-Blöbaum, J., Müller-Newen, G., Tacke, F., Yokota, Y., Zenke, M., and Hieronymus, T. (2012). Two distinct types of Langerhans cells populate the skin during steady state and inflammation. IMMUNITY 37, 905-919.