Regulation of autoimmune myocarditis by host responses to the microbiome
| Autor: | Djahida Bedja, Monica V. Talor, Guobao Chen, Daniel A. Peterson, Ashley B. Cardamone, Elizabeth Gebremariam, Daniela Cihakova, Julie Schaub, Lei Wu, Hee Sun Choi, Xuezhou Hou, SuFey Ong, Jobert G. Barin, Nicola L. Diny, Noel R. Rose |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Myocarditis Clinical Biochemistry Biology Article Autoimmune Diseases Pathology and Forensic Medicine Mice 03 medical and health sciences Immune system medicine Animals Lymphocytes Microbiome Molecular Biology Mice Knockout Autoimmune disease Mice Inbred BALB C Microbiota Innate lymphoid cell Heart Chemotaxis medicine.disease Anti-Bacterial Agents Disease Models Animal 030104 developmental biology Immunology biology.protein Dysbiosis |
| Zdroj: | Experimental and Molecular Pathology. 103:141-152 |
| ISSN: | 0014-4800 |
| Popis: | The extensive, diverse communities that constitute the microbiome are increasingly appreciated as important regulators of human health and disease through inflammatory, immune, and metabolic pathways. We sought to elucidate pathways by which microbiota contribute to inflammatory, autoimmune cardiac disease. We employed an animal model of experimental autoimmune myocarditis (EAM), which results in inflammatory and auto-immune pathophysiology and subsequent maladaptive cardiac remodeling and heart failure. Antibiotic dysbiosis protected mice from EAM and fibrotic cardiac dysfunction. Additionally, mice derived from different sources with different microbiome colonization profiles demonstrated variable susceptibility to disease. Unexpectedly, it did not track with segmented filamentous bacteria (SFB)-driven Th17 programming of CD4+ T cells in the steady-state gut. Instead, we found disease susceptibility to track with presence of type 3 innate lymphoid cells (ILC3s). Ablating ILCs by antibody depletion or genetic tools in adoptive transfer variants of the EAM model demonstrated that ILCs and microbiome profiles contributed to the induction of CCL20/CCR6-mediated inflammatory chemotaxis to the diseased heart. From these data, we conclude that sensing of the microbiome by ILCs is an important checkpoint in the development of inflammatory cardiac disease processes through their ability to elicit cardiotropic chemotaxis. |
| Databáze: | OpenAIRE |
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