TY - JOUR
T1 - Immunomodulation of Myocardial Fibrosis
AU - Sikking, Maurits A.
AU - Stroeks, Sophie L.V.M.
AU - Marelli-Berg, Federica
AU - Heymans, Stephane R.B.
AU - Ludewig, Burkhard
AU - Verdonschot, Job A.J.
N1 - Funding Information:
All figures are created with BioRender.com by Sophie Stroeks.
Publisher Copyright:
© 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - Immunotherapy is a potential cornerstone in the treatment of myocardial fibrosis. During a myocardial insult or heart failure, danger signals stimulate innate immune cells to produce chemokines and profibrotic cytokines, which initiate self-escalating inflammatory processes by attracting and stimulating adaptive immune cells. Stimulation of fibroblasts by inflammatory processes and the need to replace damaged cardiomyocytes fosters reshaping of the cardiac fibroblast landscape. In this review, we discuss new immunomodulatory strategies that manipulate and direct cardiac fibroblast activation and differentiation. In particular, we highlight immunomodulatory strategies that target fibroblasts such as chimeric antigen receptor T cells, interleukin-11, and invariant natural killer T-cells. Moreover, we discuss the potential of manipulating both innate and adaptive immune system components for the translation into clinical validation. Clearly, multiple pathways should be considered to develop innovative approaches to ameliorate myocardial fibrosis and hence to reduce the risk of heart failure.
AB - Immunotherapy is a potential cornerstone in the treatment of myocardial fibrosis. During a myocardial insult or heart failure, danger signals stimulate innate immune cells to produce chemokines and profibrotic cytokines, which initiate self-escalating inflammatory processes by attracting and stimulating adaptive immune cells. Stimulation of fibroblasts by inflammatory processes and the need to replace damaged cardiomyocytes fosters reshaping of the cardiac fibroblast landscape. In this review, we discuss new immunomodulatory strategies that manipulate and direct cardiac fibroblast activation and differentiation. In particular, we highlight immunomodulatory strategies that target fibroblasts such as chimeric antigen receptor T cells, interleukin-11, and invariant natural killer T-cells. Moreover, we discuss the potential of manipulating both innate and adaptive immune system components for the translation into clinical validation. Clearly, multiple pathways should be considered to develop innovative approaches to ameliorate myocardial fibrosis and hence to reduce the risk of heart failure.
KW - cardiomyopathy
KW - fibroblast
KW - immune
KW - immunology
KW - immunotherapy
KW - myocardial fibrosis
U2 - 10.1016/j.jacbts.2023.03.015
DO - 10.1016/j.jacbts.2023.03.015
M3 - (Systematic) Review article
SN - 2452-302X
VL - 8
SP - 1477
EP - 1488
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 11
ER -