Valvular & structural heart disease
CD301b/MGL2 + Mononuclear Phagocytes Orchestrate Autoimmune Cardiac Valve Inflammation and Fibrosis
Authors' conclusion
CD301b/MGL2+ MNPs are key drivers of autoimmune MVD in K/B.g7 mice and are also present in human rheumatic heart disease.
Study context
- Population
- K/B.g7 TCR transgenic mice with spontaneous autoimmune fibroinflammatory mitral valve (MV) disease; human rheumatic heart disease valve specimens
- Outcome
- Mechanisms of autoimmune MV disease
Methodological detailsK/B.g7 T-cell receptor transgenic mouse model, bone marrow chimeras, conditional deletion (Cx3Cr1-Cre), antibody blockade, human rheumatic heart disease specimens
- K/B.g7 T-cell receptor transgenic mouse model
- Bone marrow chimeras
- Conditional deletion (Cx3Cr1-Cre)
- Antibody blockade
- Human rheumatic heart disease specimens
Main finding
As reported in the abstract
- Mononuclear phagocytes (MNPs) (CX3CR1+, CD301b/MGL2+) comprised the vast majority of MV-infiltrating cells; analogous cells in human rheumatic heart disease valves
- Mice lacking CX3CR1 or with CD301b/MGL2+ MNPs ablated were protected from MV disease (MVD)
- CD301b/MGL2+ MNPs expressed arginase-1, resistin-like molecule α, tumor necrosis factor (TNF) and IL-6; antibody blockade of TNF and IL-6 prevented MVD
- Deleting Syk from CX3CR1+ MNPs reduced TNF and IL-6 production and prevented MVD
- TNF acted via TNF receptor-1 on valve-resident cells to increase VCAM-1 expression
- Conditional deletion of VLA-4 from CX3CR1+ MNPs prevented MVD
Original publication
CD301b/MGL2 + Mononuclear Phagocytes Orchestrate Autoimmune Cardiac Valve Inflammation and Fibrosis. Circulation. Published 31 January 2018. doi:10.
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