Abstract

Autoimmune myocarditis is a complex inflammatory response in the heart caused by abnormal immune system activity. We used modern single-cell technologies to analyze the complex gene expression patterns in autoimmune myocarditis tissue samples during several stages of inflammation: acute, subacute, and chronic. We identified the presence of T cell-monocyte complexes in both control and myocarditis samples from different phases using detailed analysis of vast single-cell RNA sequencing data. These complexes were notably more prevalent throughout the acute and subacute stages. Our investigation of gene ontology revealed their involvement in important processes as signal transduction, immune response control, and T cell proliferation and activation. We conducted a thorough analysis of trajectories, uncovering the step-by-step changes of macrophages into clusters linked to antigen presentation, oxidative stress responses, complement activation, and phagocytosis. Furthermore, our examination of neutrophil paths revealed their development and maturation from the bone marrow to distinct functional stages. Our analysis of cellular communication networks revealed consistent and phase-specific patterns, providing valuable information on how immune responses change as the disease progresses. We noted a substantial increase in BAFF signaling from normal to acute phases, while CHEMERIN signaling was upregulated from acute to chronic phases. The discoveries greatly improve our understanding of autoimmune myocarditis on a molecular level, providing a strong basis for creating personalized precision medicine treatments for each patient. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/584698v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1150607org.highwire.dtl.DTLVardef@13eb725org.highwire.dtl.DTLVardef@6a0be9org.highwire.dtl.DTLVardef@3400ac_HPS_FORMAT_FIGEXP M_FIG C_FIG