ANGPTL2 promotes immune checkpoint inhibitor-related murine autoimmune myocarditis

Use of immune checkpoint inhibitors (ICIs) as cancer immunotherapy advances rapidly in the clinic. Despite their therapeutic benefits, ICIs can cause clinically significant immune-related adverse events (irAEs), including myocarditis. However, the cellular and molecular mechanisms regulating irAE remain unclear. Here, we investigate the function of Angiopoietin-like protein 2 (ANGPTL2), a potential inflammatory mediator, in a mouse model of ICI-related autoimmune myocarditis. ANGPTL2 deficiency attenuates autoimmune inflammation in these mice, an outcome associated with decreased numbers of T cells and macrophages. We also show that cardiac fibroblasts express abundant ANGPTL2. Importantly, cardiac myofibroblast-derived ANGPTL2 enhances expression of chemoattractants via the NF-kappa B pathway, accelerating T cell recruitment into heart tissues. Our findings suggest an immunostimulatory function for ANGPTL2 in the context of ICI-related autoimmune inflammation and highlight the pathophysiological significance of ANGPTL2-mediated cardiac myofibroblast/immune cell crosstalk in enhancing autoimmune responses. These findings overall provide insight into mechanisms regulating irAEs. Cardiac fibroblast-derived ANGPTL2 plays a role in immune checkpoint inhibitors -related autoimmune myocarditis by enhancing chemokine-induced recruitment of T cells.

Automated summary

This study investigates the role of Angiopoietin-like protein 2 (ANGPTL2) in ICI-related autoimmune myocarditis and demonstrates its immunostimulatory function in promoting T cell recruitment. These findings provide insight into the mechanisms regulating irAEs and highlight the importance of cardiac myofibroblast/immune cell crosstalk in enhancing autoimmune responses.