01. June 2017

ERC Starting Grant for allergy research in the gut

ROR(?t)+ Tregs: Costained Foxp3 (nucleus in red) and ROR(?t) (reporter in cytoplasm, green) in the lamina propria of the large intestine. Source: Helmholtz Zentrum München

The European Research Council (ERC) will be funding the ALLERGUT project at the Helmholtz Zentrum München for the next five years with an ERC Starting Grant. Working in this framework, the researchers headed by Dr. Caspar Ohnmacht want to discover if and how bacteria in the intestines can assist or prevent the development of allergies. The total funding amounts to 1.5 million euros.

It is estimated that almost one out of three people in Europe suffers from one or more allergic diseases. Because the underlying mechanisms continue to be only superficially understood, current treatment forms can only alleviate the symptoms. The objective of the EU-funded ALLERGUT project is to explain why allergic reactions develop in the first place. As the name suggests, the search for allergy causes is focused primarily on the gut.

Project leader Caspar Ohnmacht and his team particularly want to take a close look at the interplay between the intestinal flora and the immune system. "The central element in our investigations will be the protein ROR?t*," explains the head of the Mucosal Immunology Research Group at the Center of Allergy & Environment (ZAUM), Helmholtz Zentrum München and Technical University of Munich. He has spent years studying inflammatory processes that originate in the digestive system.

ROR?t is a so-called transcription factor that, in the cell nucleus, can influence the expression of genes. Ohnmacht and his team have already been able to show that bacterial colonisation of the gut causes immune cells to produce ROR?t there. As a result, immunological tolerance develops. This denotes the immune system's ability to distinguish its own structures and harmless foreign structures, such as gut bacteria or allergens, from pathogens and to tolerate their presence. ROR?t particularly acts in the so-called regulatory T cells (Tregs) in the gut, which curb the immune system and ensure that excessive immune responses are avoided.

In the coming five years, Ohnmacht and his team want to examine a number of aspects in this regard. For instance, they want to determine what influence ROR?t has on the development of allergy-triggering immune cells in the intestinal mucosa and also on other superficial organs. They are particularly interested in Treg-mediated tolerance.

“We are also going to study the question of which signalling pathways in the dendritic cells, which are cells that constantly monitor their environment, regulate the establishment of this type of tolerance,” explains Ohnmacht. The Helmholtz researchers would also like to clarify if there are certain bacterial or metabolic groups that support an allergic predisposition. “If we succeed here, it would be a giant step toward understanding why allergies and other chronic inflammatory diseases triggered by insufficient tolerance develop in the first place. This could make new preventive measures and the development of new treatment concepts possible in the future.”