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New insights into the immune system of the gastrointestinal tract

Lymphotoxin is a cytokine, or intercellular messenger, and plays an important role in the immunological balance of the gastrointestinal tract.

It regulates the immune system of the digestive tract, which is made up of immune cells, immunoglobulins (antibodies) as well as intestinal bacteria.

An international team of scientists supported by the Helmholtz Zentrum München has now discovered how this complex interaction functions and how lymphotoxin controls the production of immunoglobulins in the gut. The results are published in the latest issue of the specialist journal Science.

New insights into the immune system of the gastrointestinal tract
Image: Prof. Mathias Heikenwälder (Source: Helmholtz Zentrum München)
Naturally occurring intestinal bacteria (also known as gut flora) and an immune system comprising local immune cells maintain the immunological balance in the gastrointestinal tract. One important agent is immunoglobulin A (IgA), which is found on mucous membranes, where it renders pathogens and toxins harmless.

Lymphotoxins control the production of immunoglobulin A (IgA) and thus participate in immune responses as well as in the regular composition of the intestinal flora, the scientists report in the study. The team led by Dr. Andrey Kruglov and Professor Sergei Nedospasov from the German Rheumatism Research Center (DRFZ) Berlin, an institute of the Leibniz Association, Professor Mathias Heikenwälder from the Institute of Virology at the Helmholtz Zentrum München (HMGU) as well as other national and international partners were able to show that lymphotoxins – soluble lymphotoxin alpha (sLTa3) as well as membrane-bound lymphotoxin beta (LTa1b2) – induce IgA production and support the body’s immune response. Lymphotoxins are inflammatory messengers that are formed by immune cells when they come into contact with pathogens. If these lymphotoxins are lacking, IgA production is reduced or even halted, resulting in changes in the intestinal flora.

“The results provide us with new insights into how the enteric immune system functions. The relationship between inflammatory messengers and the performance of the immune system helps us to understand how intestinal diseases occur“, Professor Heikenwälder explains. He adds another important relevance of their results: “These insights are also important for the treatment with certain immunomodulators (such as tumor necrosis factor alpha (TNF) blockers, e.g. etanercept). They bind soluble lymphotoxin and could therefore also influence IgA production and as a result upset the immunological balance.”

Further Information

Original publication:
Kruglov, A. et al. (2013), Nonredundant Function of Soluble LTa3 Produced by Innate Lymphoid Cells in Intestinal Homeostasis. Science, doi: 10.1126/science.1243364

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,200 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members.

Scientific contact
Prof. Mathias Heikenwälder, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute of Virology, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany – Tel. +49 89 4140-7440

Mathias Heikenwälder | EurekAlert!
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