| First Author | Horiguchi H | Year | 2023 |
| Journal | Commun Biol | Volume | 6 |
| Issue | 1 | Pages | 965 |
| PubMed ID | 37736764 | Mgi Jnum | J:340727 |
| Mgi Id | MGI:7530078 | Doi | 10.1038/s42003-023-05338-4 |
| Citation | Horiguchi H, et al. (2023) ANGPTL2 promotes immune checkpoint inhibitor-related murine autoimmune myocarditis. Commun Biol 6(1):965 |
| abstractText | 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-kappaB 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. |
