Ineffective Helper Cells

IKBNS has a crucial impact on the effect and function of Th17 cells

The infiltration of immune cells into the mucous membrane of the mouse colon was detected after chemical-induced colitis by means of hematoxylin and eosin staining.The IKBNS protein is very important for the development of immune cells: Two years ago, it was discovered that regulatory T cells, so-called Tregs, do not develop in the absence of this protein. The IKBNS protein also plays a role in the development of another type of cell, i.e. Th 17 cells. Scientists working at the Helmholtz Centre for Infection Research (HZI) in Braunschweig have shown that these helper cells, unlike Tregs, develop in the absence of the protein, but remain ineffective. In the long term, the results published in the "Journal of Immunology" might be helpful in the treatment of autoimmune diseases.

T cells are a group of white blood cells that make a major contribution to the body's inherent immune response. There are various types of T cells that take on different functions in the immune reaction. The so-called T helper cells control the immune response by stimulating the growth and differentiation of immune cells. Special messenger substances called cytokines are released for this purpose. A sub-type of T helper cells called Th17 cells produces a cytokine called interleukin 17.

These cells play an important role not only in the defence against extracellular pathogens, such as bacteria, but can also have a detrimental effect. "In autoimmune diseases they promote tissue damage," says Prof Ingo Schmitz, head of the "System-oriented Immunology and Inflammation Research" research group at the HZI. "It is therefore exciting to learn exactly how they are made and what causes them to be made."

Searching for an answer, he and his colleagues from the TWINCORE in Hannover and the Charité in Berlin applied an approach that was used previously with other T cells. "Two years ago, we showed that the IKBNS protein plays a key role in the development of Tregs," says Schmidt. Switch the protein off and no Tregs are made any longer. They then no longer regulate the immune response and, in the worst case, the defence system over-reacts significantly. The results of the researchers demonstrate: The case is different with Th17 cells.

"Even if IKBNS is switched off completely, Th17 cells can still differentiate. But we observed that the cells proliferate more slowly and produce less cytokine overall," says Schmidt. This has an impact on the effectiveness of Th17 cells: If IKBNS was switched off in a mouse model, no Th17 cells developed any more during a chronic bowel inflammation. Moreover, the immune response to Citrobacter rodentium - a bacterium that is related to E. coli bacteria, which are pathogenic to humans - is reduced and the bacteria survived.

This means that IKBNS is not solely responsible for the differentiation of Th17 cells, which is in contrast to Tregs, but it still has a decisive influence on the proper functioning of the immune cells.

"In the long term, these findings might help us find new starting points for the treatment of autoimmune and infectious diseases. If IKBNS can be manipulated specifically in certain T cells, then it might be possible to tailor the immune response to the corresponding infection or autoimmune disorder," says Schmidt. This research is being continued at the "Molecular Organisation of Cellular Communication in the Immune System" (SFB 854) department at the Otto-von-Guericke University in Magdeburg.

Original publication:

Michaela Annemann, Zuobai Wang, Carlos Plaza-Sirvent, Rainer Glauben, Marc Schuster, Frida Ewald Sander, Panagiota Mamareli, Anja A. Kühl, Britta Siegmund, Matthias Lochner and Ingo Schmitz (2015). IκBNS Regulates Murine Th17 Differentiation during Gut Inflammation and Infection. The Journal of Immunology, DOI: 10.4049/​jimmunol.1401964.

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