Heart-Specific Immune Responses in an Animal Model of Autoimmune-Related Myocarditis Mitigated by an Immunoproteasome Inhibitor and Genetic Ablation | Zendy

Mariella Bockstahler | Zendy; Andrea Fischer | Zendy; Carl Christoph Goetzke | Zendy; Hannah Louise Neumaier | Zendy; Martina Sauter | Zendy; Meike Kespohl | Zendy; AnnaMaria Müller | Zendy; Christin Meckes | Zendy; Christian Salbach | Zendy; Mirjam Schenk | Zendy; Arnd Heuser | Zendy; Ulf Landmesser | Zendy; January Weiner | Zendy; Benjamin Meder | Zendy; Lorenz Lehmann | Zendy; Adelheid Kratzer | Zendy; Karin Klingel | Zendy; Hugo A. Katus | Zendy; Ziya Kaya | Zendy; Antje Beling | Zendy

Open Access

Heart-Specific Immune Responses in an Animal Model of Autoimmune-Related Myocarditis Mitigated by an Immunoproteasome Inhibitor and Genetic Ablation

Author(s) -

Mariella Bockstahler,

Andrea Fischer,

Carl Christoph Goetzke,

Hannah Louise Neumaier,

Martina Sauter,

Meike Kespohl,

AnnaMaria Müller,

Christin Meckes,

Christian Salbach,

Mirjam Schenk,

Arnd Heuser,

Ulf Landmesser,

January Weiner,

Benjamin Meder,

Lorenz Lehmann,

Adelheid Kratzer,

Karin Klingel,

Hugo A. Katus,

Ziya Kaya,

Antje Beling

Publication year - 2020

Publication title -

circulation

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 7.795

H-Index - 607

eISSN - 1524-4539

pISSN - 0009-7322

DOI - 10.1161/circulationaha.119.043171

Subject(s) - myocarditis , immunology , medicine , immune system , proinflammatory cytokine , autoimmunity , autoimmune disease , inflammation , antibody

Immune checkpoint inhibitor (ICI) therapy is often accompanied by immune-related pathology, with an increasing occurrence of high-risk ICI-related myocarditis. Understanding the mechanisms involved in this side effect could enable the development of management strategies. In mouse models, immune checkpoints, such as PD-1 (programmed cell death protein 1), control the threshold of self-antigen responses directed against cardiac TnI (troponin I). We aimed to identify how the immunoproteasome, the main proteolytic machinery in immune cells harboring 3 distinct protease activities in the LMP2 (low-molecular-weight protein 2), LMP7 (low-molecular-weight protein 7), and MECL1 (multicatalytic endopeptidase complex subunit 1) subunit, affects TnI-directed autoimmune pathology of the heart.

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