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The messenger molecule interleukin 17 (IL-17) does not contribute directly to the development of multiple sclerosis (MS) in the central nervous system (CNS). However, IL-17 does influence the development of experimental autoimmune encephalomyelitis (EAE), the animal model for MS, through the gut microbiome. Current therapies against chronic-inflammatory autoimmune diseases, which target the biological function of IL-17, must therefore be considered with caution due to potential long-term adverse effects on intestinal health. Scientists of the University Medical Center Mainz have now published these important findings in the current issue of the renowned journal “Science Immunology”.
Scientists of the University Medical Center Mainz document a relationship between autoimmune disease and the gut microbiome
Which role does the messenger molecule interleukin 17 (IL-17) play in the development of the autoimmune disease multiple sclerosis (MS)? The current consensus is that IL-17 participates at the front-line, i.e. directly in the central nervous system (CNS) during disease progression, yet this view is also controversial as some researchers rate the role of this messenger molecule as rather low. Dr. Tommy Regen and his team leader Univ.-Prof. Dr. Ari Waisman, director of the Institute of Molecular Medicine at the University Medical Center Mainz, attempt to explain this discrepancy through their study “IL-17 controls central nervous system autoimmunity through the intestinal microbiome”, now published in “Science Immunology”.
In experimental autoimmune encephalomyelitis (EAE), the animal model for MS, cells of the immune system, specifically T cells, are responsible for triggering the chronic inflammation underlying this neurologic autoimmune disease. Exactly those T cells are also among the major producers of IL-17, in the mouse as well as in man. IL-17-producing T cells have been shown to play a pivotal role in the development of MS. Therefore, parts of the research community have come to the conclusion that IL-17 itself is fundamental to disease development in the CNS.
As was now shown by the researchers of the Institute of Molecular Medicine at the University Medical Center Mainz, mice that are deficient for IL-17 surprisingly lose their susceptibility to develop EAE – they don’t get sick. Regardless of that fact, their T cells nevertheless carry the potential to induce CNS inflammation. This result led the research team to conclude that, at least in the animal model, the messenger IL-17 itself is not directly involved in the development of the neurologic autoimmune disease MS within the CNS.
Another remarkable observation was made by the study team: an indirect effect of IL-17. The gut microflora of animals lacking this messenger molecule underwent strong alterations and this in turn rendered the animals resistant to the EAE development. By manipulating the gut microflora, specifically using a targeted supplementation of the gut with IL-17, the researchers provoked changes in the immune system, which rendered these mice susceptible again to develop EAE. Hence it is the expression in the gut and not its effector function in the CNS that connects IL-17 with EAE susceptibility.
With their findings, Dr. Regen et al. substantiate an essential role for IL-17 in maintaining a healthy gut. They further demonstrate that there is a direct connection between the gut microbiota composition and the potential to develop autoimmune diseases like MS. With this, their research provides an important stimulus for future investigations.
Moreover, these research achievements are relevant for the treatment of other inflammatory diseases, like psoriasis, rheumatoid arthritis or some cardiovascular conditions. In these diseases, many patients have benefited from treatments that target the neutralization of IL-17. The new research results indicate, however, that the long-term effects of such treatments should at least be monitored in order to exclude a negative impact on the intestinal health in these patients.
Original publication:
IL-17 controls central nervous system autoimmunity through the intestinal microbiome;
Tommy Regen, Sandrine Isaac, Ana Amorim, Nicolás Gonzalo, Judith Hauptmann, Arthi Shanmugavadivu, Matthias Klein, Roman Sankowski, Ilgiz A Mufazalov, Nir Yogev, Jula Huppert, Florian Wanke, Michael Witting, Alexandra Grill, Eric J C Gálvez, Alexei Nikolaev, Michaela Blanfeld, Immo Prinz, Philippe Schmitt-Kopplin, Till Strowig, Christoph Reinhardt, Marco Prinz, Tobias Bopp, Burkhard Becher, Carles Ubeda, Ari Waisman;
Science Immunology, 05 Feb 2021; Vol. 6, Issue 56, eaaz6563;
DOI: 10.1126/sciimmunol.aaz6563
Caption: Bacteria (red) in direct contact to cells of the intestinal wall (green, cell nuclei in blue).
Image Source: University Medical Center Mainz
Contact
Univ.-Prof. Dr. Ari Waisman
Director Institute of Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, Germany,
phone: +49 6131-17 9129; e-mail: waisman@uni-mainz.de
Press contact:
Barbara Reinke
Corporate Communications, University Medical Center Mainz
Langenbeckstr. 1, 55131 Mainz, Germany,
phone +49 6131 17-7428, fax +49 6131 17-3496; e-mail: pr@unimedizin-mainz.de
www.unimedizin-mainz.de
About the University Medical Center of Johannes Gutenberg University Mainz
The University Medical Center of Johannes Gutenberg University Mainz (JGU) is the only medical institution of supra-maximum supply in Rhineland-Palatinate and an internationally recognized science location. It comprises more than 60 clinics, institutes, and departments working interdisciplinarily. Highly specialized patient care, research, and teaching form an inseparable unit in the University Medical Center Mainz. Around 3,400 students of medicine and dentistry are trained in Mainz. With approximately 8,500 employees, the University Medical Center Mainz is also one of the largest employers in the region and an important driver of growth and innovation. Further information is available online at www.unimedizin-mainz.de.
Univ.-Prof. Dr. Ari Waisman
Director Institute of Molecular Medicine, University Medical Center of the Johannes Gutenberg University of Mainz, Germany,
phone: +49 6131-17 9129; e-mail: waisman@uni-mainz.de
IL-17 controls central nervous system autoimmunity through the intestinal microbiome;
Tommy Regen, Sandrine Isaac, Ana Amorim, Nicolás Gonzalo, Judith Hauptmann, Arthi Shanmugavadivu, Matthias Klein, Roman Sankowski, Ilgiz A Mufazalov, Nir Yogev, Jula Huppert, Florian Wanke, Michael Witting, Alexandra Grill, Eric J C Gálvez, Alexei Nikolaev, Michaela Blanfeld, Immo Prinz, Philippe Schmitt-Kopplin, Till Strowig, Christoph Reinhardt, Marco Prinz, Tobias Bopp, Burkhard Becher, Carles Ubeda, Ari Waisman;
Science Immunology, 05 Feb 2021; Vol. 6, Issue 56, eaaz6563;
DOI: 10.1126/sciimmunol.aaz6563
Bacteria (red) in direct contact to cells of the intestinal wall (green, cell nuclei in blue)
University Medical Center Mainz
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Bacteria (red) in direct contact to cells of the intestinal wall (green, cell nuclei in blue)
University Medical Center Mainz
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