CD301b/MGL2 ⁺ Mononuclear Phagocytes Orchestrate Autoimmune Cardiac Valve Inflammation and Fibrosis

Abstract

CD301b/MGL2 MNPs are key drivers of autoimmune MVD in K/B.g7 mice and are also present in human rheumatic heart disease. We define key inflammatory molecules that drive MVD in this model, including Syk, TNF, interleukin-6, very late antigen-4, and vascular cell adhesion molecule-1.

Adaptive immune cells in calcific aortic valve disease

“…Although this is not a study of CAVD, this finding suggests a tendency in inflammatory states for proinflammatory T lymphocytes to accumulate in the AV in chronic inflammatory states, echoing the cardiac tropism seen in PD-1-deficient mice. Finally, macrophages and monocytes play a key role in rheumatic valve fibrosis (113). Although this disease model is not the same as CAVD, some insight can be taken from the way that macrophages direct this process of valvular fibrosis.…”

The Contribution of Autoantibodies to Inflammatory Cardiovascular Pathology

“…These results support a model whereby circulating IgG AAbs mediate cardiac inflammation through macrophage activation downstream of activating FcγR-mediated recognition of circulating IgG AAbs. Additional studies employing conditional gene deletions to dissect the key functional consequences induced in macrophages following IgG AAb recognition have provided important insight into mechanisms by which AAbs contribute to experimental VHD ( 162 ). Samples from patients with RHD were used to demonstrate correlations of the authors’ experimental observations to human inflammatory VHD.…”

Myeloid Cells Remodel the Mitral Valve

“…In this issue of Circulation 2 , Meier et al describe for the first time the causal involvement of innate immune cells in the pathogenesis of mitral valve disease. The authors conducted their studies in K/B.g7 T cell receptor transgenic mice (TCR mice) which express a T-cell receptor that recognizes the self-peptide glucose-6-phosphate isomerase.…”

“…While the detection of cardiac leukocytes with standard immunohistochemistry techniques was often hampered by limited sensitivity, improvements in imaging technology now enable analysis of leukocyte subsets and phenotypes in much more detail. Using optical tissue clearing procedures prior to whole-mount imaging of mitral valves in combination with myeloid cell-specific expression of fluorescent proteins, the current manuscript 2 visualizes myeloid cells in mitral valves of TCR mice. Their abundance in valve tissues is further corroborated by flow cytometric analysis of inflammatory cells in excised mitral valves.…”