Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases

Cells

Zlatko Trajanoski¹  Gregor Sturm¹  Michael Schumann²  Raja Atreya³  Marvin Bubeck³  Miguel Gonzalez Acera³  Markus F. Neurath³  Christoph Becker³  Jay V. Patankar³  Leonard Diemand³  Fabrizio Mascia³  Christoph S.N. Klose⁴  Dieter Chichung Lie⁵  Anja A. Kühl⁶ 

[1] Biocenter, Institute of Bioinformatics, Medical University Innsbruck, 6020 Innsbruck, Austria;Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany;Department of Medicine 1, University of Erlangen-Nuremberg, 91052 Erlangen, Germany;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;Institut für Biochemie, Emil-Fischer-Zentrum, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany;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;

关键词: enteric nervous system;    neurogenesis;    inflammatory bowel diseases;    ulcerative colitis;    Crohn’s disease;   

DOI  :  10.3390/cells10092253

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown