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Research group "Mucosal defense"

Head of the research group
 

Wehkamp-WEB

Prof. Dr. med. Jan Wehkamp
Tel. +49 7071 29-82714
Fax +49 7071 29-2095

 Profile (German language)

 
Focus

The Wehkamp study group is investigating the body’s own protective immune response on different surfaces of the intestinal tract. We – humans and all other eukaryotes – only survive against micro-organisms because we are protected through a permanent and complex system of different endogenous, antimicrobial substances. Without this protection, we would very quickly be “overrun” by micro-organisms having the ability to penetrate the mucosa and the body, especially via the intestine. Survival without this system is not possible. The principle of an antimicrobial immune system has hardly changed through evolution, and we humans are hardly any different from dinosaurs, apples, ants and house plants. In humans, the so-called defensins form the main group of antimicrobial peptides. Besides these, however, there are numerous other substances with an antibacterial effect, but which were previously unknown. This was partly due to the fact that we were unaware of their antibacterial effect; only now are we beginning to understand their function with respect to their protective properties. The interplay of the defensins regulates the composition of the microflora. For example, Paneth’s granular cells in the small intestine are made up of very high quantities of α-defensins, which regulate a certain composition of the microflora and ensure that the bacteria can only colonise the intestinal crypts within certain bounds.

In inflammatory intestinal diseases such as Crohn’s disease and ulcerous colitis, this system is disturbed on account of various mechanisms, which in our perspective represents the decisive pathophysiological mechanism. Our research work in particular was able to make long-term contributions towards changing the international understanding of these diseases. Earlier, the term autoimmune disease was used in a general sense, a classification that can now be regarded as outdated. The immune system is not reacting excessively, but is in principle responding normally to the non-physiological penetration of bacteria due to a disturbed barrier function. In cases where there is inflammation of the small intestine, particularly with Crohn’s disease, but also with graft vs. host reactions following transplants, defects in Paneth’s granular cells are the main focus of international research. Moreover, there are other defects in the inducibility or constitutive expression of other antimicrobial substances. Another important disease principle has to do with the defective mucus barrier. The so-called mucins are negatively charged mucus substances that are produced by goblet cells and hold the positively charged antimicrobial peptides in the mucus when the intestine is healthy. In ulcerous colitis, this mucus layer is reduced, and sufficient quantities of antimicrobial substances cannot be kept on the surface. The result is a change in the microflora and a penetration of micro-organisms into the mucosa. While the inflammation that results from the penetration of the microflora is the (in part successful) objective of current symptom-based therapy, it is of a secondary nature (see illustration).

 

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The study group is focusing on the mechanisms of various defects in inflammatory and infectious diseases and is seeking to better understand the regulation and function of antimicrobial endogenous substances. In addition, we are identifying hitherto unknown antimicrobial substances and fragments. The objective is to establish a new supplementary therapy principle of reinforcing the body’s own protection.

 

Team

Here you can find the members of our research group

Team (German language)

Funding
Crohn-Vereinigung
Heisenberg
Emmy-Noether-Programm
erc
 

 






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