Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases
Miguel Gonzalez Acera,
Marvin Bubeck,
Fabrizio Mascia,
Leonard Diemand,
Gregor Sturm,
Anja A. Kühl,
Raja Atreya,
Dieter Chichung Lie,
Markus F. Neurath,
Michael Schumann,
Christoph S.N. Klose,
Zlatko Trajanoski,
Christoph Becker,
Jay V. Patankar
Affiliations
Miguel Gonzalez Acera
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Marvin Bubeck
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Fabrizio Mascia
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Leonard Diemand
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Gregor Sturm
Biocenter, Institute of Bioinformatics, Medical University Innsbruck, 6020 Innsbruck, Austria
Anja A. Kühl
iPATH.Berlin Histopathology Core Unit, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, 12203 Berlin, Germany
Raja Atreya
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Dieter Chichung Lie
Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
Markus F. Neurath
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Michael Schumann
Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany
Christoph S.N. Klose
Department of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Hindenburgdamm 30, 12203 Berlin, Germany
Zlatko Trajanoski
Biocenter, Institute of Bioinformatics, Medical University Innsbruck, 6020 Innsbruck, Austria
Christoph Becker
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Jay V. Patankar
Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany
Inflammatory bowel diseases (IBD) are characterized by chronic dysregulation of immune homeostasis, epithelial demise, immune cell activation, and microbial translocation. Each of these processes leads to proinflammatory changes via the release of cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), respectively. The impact of these noxious agents on the survival and function of the enteric nervous system (ENS) is poorly understood. Here, we show that in contrast to an expected decrease, experimental as well as clinical colitis causes an increase in the transcript levels of enteric neuronal and glial genes. Immunostaining revealed an elevated neuronal innervation of the inflamed regions of the gut mucosa. The increase was seen in models with overt damage to epithelial cells and models of T cell-induced colitis. Transcriptomic data from treatment naïve pediatric IBD patients also confirmed the increase in the neuroglial genes and were replicated on an independent adult IBD dataset. This induction in the neuroglial genes was transient as levels returned to normal upon the induction of remission in both mouse models as well as colitis patients. Our data highlight the dynamic and robust nature of the enteric nervous system in colitis and open novel questions on its regulation.