T cell costimulation blockade blunts pressure overload-induced heart failure

Marinos Kallikourdis (), Elisa Martini, Pierluigi Carullo, Claudia Sardi, Giuliana Roselli, Carolina M. Greco, Debora Vignali, Federica Riva, Anne Marie Ormbostad Berre, Tomas O. Stølen, Andrea Fumero, Giuseppe Faggian, Elisa Di Pasquale, Leonardo Elia, Cristiano Rumio, Daniele Catalucci, Roberto Papait and Gianluigi Condorelli ()
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Marinos Kallikourdis: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center
Elisa Martini: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center
Pierluigi Carullo: Humanitas Clinical and Research Center
Claudia Sardi: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center
Giuliana Roselli: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center
Carolina M. Greco: Humanitas Clinical and Research Center
Debora Vignali: Adaptive Immunity Laboratory, Humanitas Clinical and Research Center
Federica Riva: Università degli Studi di Milano
Anne Marie Ormbostad Berre: KG Jebsen Centre of Medicine, Norwegian University of Science and Technology
Tomas O. Stølen: KG Jebsen Centre of Medicine, Norwegian University of Science and Technology
Andrea Fumero: Cardiac Surgery, Humanitas Clinical and Research Center
Giuseppe Faggian: University of Verona
Elisa Di Pasquale: Humanitas Clinical and Research Center
Leonardo Elia: Humanitas Clinical and Research Center
Cristiano Rumio: Università degli Studi di Milano
Daniele Catalucci: Institute of Genetic and Biomedical Research (IRGB)—UOS of Milan, National Research Council of Italy
Roberto Papait: Humanitas Clinical and Research Center
Gianluigi Condorelli: Humanitas University

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Heart failure (HF) is a leading cause of mortality. Inflammation is implicated in HF, yet clinical trials targeting pro-inflammatory cytokines in HF were unsuccessful, possibly due to redundant functions of individual cytokines. Searching for better cardiac inflammation targets, here we link T cells with HF development in a mouse model of pathological cardiac hypertrophy and in human HF patients. T cell costimulation blockade, through FDA-approved rheumatoid arthritis drug abatacept, leads to highly significant delay in progression and decreased severity of cardiac dysfunction in the mouse HF model. The therapeutic effect occurs via inhibition of activation and cardiac infiltration of T cells and macrophages, leading to reduced cardiomyocyte death. Abatacept treatment also induces production of anti-inflammatory cytokine interleukin-10 (IL-10). IL-10-deficient mice are refractive to treatment, while protection could be rescued by transfer of IL-10-sufficient B cells. These results suggest that T cell costimulation blockade might be therapeutically exploited to treat HF.

Date: 2017
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DOI: 10.1038/ncomms14680

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