Zinc inhibits lethal inflammatory shock by preventing microbe‐induced interferon signature in intestinal epithelium

EMBO Molecular Medicine

卷:12

Tineke Vanderhaeghen¹  Steven Timmermans¹  Tino Hochepied¹  Claude Libert¹  Sylviane Dewaele¹  Rudi Beyaert¹  Marlies Ballegeer¹  Melanie Eggermont¹  Sofie Vandevyver¹  Kelly Van Looveren¹  Jolien Vandewalle¹  Charlotte Wallaeys¹  Lindsy Aelbrecht¹  Jolien Souffriau¹  Riet De Rycke²  Michiel De Bruyne²  Raul Tito³  Jeroen Raes³  Lindsey De Commer³  Serge Verbanck⁴  Filip Van Immerseel⁴  Filip Boyen⁴  Evy Goossens⁴  Tiago Velho⁵  Luis Ferreira Moita⁵  Karolien De Bosscher⁶ 

[1] Center for Inflammation Research VIB Ghent Belgium;

[2] Department of Biomedical Molecular Biology and Expertise Centre for Transmission Electron Microscopy Ghent University Ghent Belgium;

[3] Department of Microbiology and Immunology Rega Institute, KU Leuven Leuven Belgium;

[4] Department of Pathology, Bacteriology and Avian Diseases Faculty of Veterinary Medicine Ghent University Merelbeke Belgium;

[5] Instituto Gulbenkian de Ciência Oeiras Portugal;

[6] VIB Center for Medical Biotechnology Ghent Belgium;

关键词: genetics;    inflammation;    microbiota;    nutrient;    regulation;   

DOI  :  10.15252/emmm.201911917

来源: DOAJ

【 摘 要 】

Abstract The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF‐induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which lack glucocorticoids (GCs), or express mutant versions of their receptor GR in IECs, nor in mice which lack gut microbiota. RNA‐seq studies in IECs showed that zinc caused reduction in expression of constitutive (STAT1‐induced) interferon‐stimulated response (ISRE) genes and interferon regulatory factor (IRF) genes. Since some of these genes are involved in TNF‐induced cell death in intestinal crypt Paneth cells, and since zinc has direct effects on the composition of the gut microbiota (such as several Staphylococcus species) and on TNF‐induced Paneth cell death, we postulate a new zinc‐related anti‐inflammatory mechanism. Zinc modulates the gut microbiota, causing less induction of ISRE/IRF genes in crypt cells, less TNF‐induced necroptosis in Paneth cells, and less fatal evasion of gut bacteria into the system.

【 授权许可】

Unknown