Nature https://doi.org/10.1038/s41586-019-1546-z (2019)

After injury, cardiac fibroblasts induce cardiac fibrosis, which is an important factor in the progression of cardiac disease. In Nature, Epstein and colleagues use T cell immunotherapy to limit cardiac fibrosis in a mouse model of cardiac injury. Mice that express ovalbumin peptide in activated cardiac fibroblasts, but not in quiescent cardiac fibroblasts, and have received ovalbumin-specific CD8+ OT-I T cells develop less cardiac fibrosis than do their counterparts not given T cell transfer. The authors show that the endogenous glycoprotein FAP is not expressed in healthy hearts or other tissues in mice and humans but is expressed in cardiac fibroblasts in patients with cardiomyopathy. Injured mice given transfer of T cells engineered to express a chimeric antigen receptor (CAR T cells) directed against FAP have less fibrosis than that of injured mice that did not receive CAR T cells, and also show partial restoration of heart function. FAP CAR T cell therapy shows no evidence of systemic or cardiac toxicity and does not delay wound healing in a model of skin injury.