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| Status |
Public on Aug 01, 2021 |
| Title |
Cardiac fibroblasts regulate macrophage ontogeny, phenotype and function during cardiac injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Two types of monocytes, inflammatory and patrolling, infiltrate the hearts in both human myocarditis and murine experimental autoimmune myocarditis (EAM) model. The fates and functions of these infiltrating monocytes governing the progression of heart failure remain unclear. Here, we created parabiotic EAM and naïve mice to show that cardiac inflammation facilitate monocyte-to-macrophage differentiation. Using a combination of flow cytometry, time lapsed imaging and transmission electron microscopy, we demonstrated in vitro that cardiac fibroblasts interact with monocytes and are instrumental in facilitating monocyte-to-macrophage differentiation. Moreover, IL-17A stimulated cardiac fibroblasts completely arrested Ly6Clo monocyte proliferation and inhibited both Ly6Chi and Ly6Clo monocyte-to-macrophage differentiation both in vitro and in vivo after intracardiac injections of monocytes into the hearts. Intriguingly, IL-17A signaling through cardiac fibroblasts also significantly downregulated Mer tyrosine kinase (MerTK) expressions on Ly6Chi monocyte-derived macrophages, thus jeopardizing their phagocytic abilities. Collectively, our results implicate divergent fates and functions of heart-infiltrating monocytes influenced by cardiac fibroblasts.
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| Overall design |
Splenic Ly6Chi monocytes and Ly6Clo monocytes were co-cultured with cardiac fibroblasts with or without IL-17A stimulation for approximately 160 hours, biological triplicates of each conditions that resulted in monocyte-derived macrophages were then FACS sorted and subjected to microarray analysis, total samples n=9
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| Contributor(s) |
Hou X, Čiháková D |
| Citation(s) |
31269438 |
| Submission date |
Aug 21, 2018 |
| Last update date |
Nov 01, 2021 |
| Contact name |
Daniela Cihakova M.D. Ph.D. D(ABMLI) |
| Organization name |
The Johns Hopkins University School of Medicine
|
| Department |
Pathology-Immunopathology
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| Street address |
720 Rutland Avenue
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21205 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA487063 |
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