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Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis

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Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis. / Zarak-Crnkovic, Martina; Kania, Gabriela; Jaźwa-Kusior, Agnieszka; Czepiel, Marcin; Wijnen, Winandus J; Czyż, Jarosław; Müller-Edenborn, Björn; Vdovenko, Daria; Lindner, Diana; Gil-Cruz, Cristina; Bachmann, Marta; Westermann, Dirk; Ludewig, Burkhard; Distler, Oliver; Lüscher, Thomas F; Klingel, Karin; Eriksson, Urs; Błyszczuk, Przemysław.

In: BASIC RES CARDIOL, Vol. 115, No. 1, 20.12.2019, p. 6.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Zarak-Crnkovic, M, Kania, G, Jaźwa-Kusior, A, Czepiel, M, Wijnen, WJ, Czyż, J, Müller-Edenborn, B, Vdovenko, D, Lindner, D, Gil-Cruz, C, Bachmann, M, Westermann, D, Ludewig, B, Distler, O, Lüscher, TF, Klingel, K, Eriksson, U & Błyszczuk, P 2019, 'Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis', BASIC RES CARDIOL, vol. 115, no. 1, pp. 6. https://doi.org/10.1007/s00395-019-0766-6

APA

Zarak-Crnkovic, M., Kania, G., Jaźwa-Kusior, A., Czepiel, M., Wijnen, W. J., Czyż, J., Müller-Edenborn, B., Vdovenko, D., Lindner, D., Gil-Cruz, C., Bachmann, M., Westermann, D., Ludewig, B., Distler, O., Lüscher, T. F., Klingel, K., Eriksson, U., & Błyszczuk, P. (2019). Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis. BASIC RES CARDIOL, 115(1), 6. https://doi.org/10.1007/s00395-019-0766-6

Vancouver

Zarak-Crnkovic M, Kania G, Jaźwa-Kusior A, Czepiel M, Wijnen WJ, Czyż J et al. Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis. BASIC RES CARDIOL. 2019 Dec 20;115(1):6. https://doi.org/10.1007/s00395-019-0766-6

Bibtex

@article{61c21fe711de419880c3d413c2682041,
title = "Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis",
abstract = "Heart-specific CD4+ T cells have been implicated in development and progression of myocarditis in mice and in humans. Here, using mouse models of experimental autoimmune myocarditis (EAM) we investigated the role of heart non-specific CD4+ T cells in the progression of the disease. Heart non-specific CD4+ T cells were obtained from DO11.10 mice expressing transgenic T cell receptor recognizing chicken ovalbumin. We found that heart infiltrating CD4+ T cells expressed exclusively effector (Teff) phenotype in the EAM model and in hearts of patients with lymphocytic myocarditis. Adoptive transfer experiments showed that while heart-specific Teff infiltrated the heart shortly after injection, heart non-specific Teff effectively accumulated during myocarditis and became the major heart-infiltrating CD4+ T cell subset at later stage. Restimulation of co-cultured heart-specific and heart non-specific CD4+ T cells with alpha-myosin heavy chain antigen showed mainly Th1/Th17 response for heart-specific Teff and up-regulation of a distinct set of extracellular signalling molecules in heart non-specific Teff. Adoptive transfer of heart non-specific Teff in mice with myocarditis did not affect inflammation severity at the peak of disease, but protected the heart from adverse post-inflammatory fibrotic remodelling and cardiac dysfunction at later stages of disease. Furthermore, mouse and human Teff stimulated in vitro with common gamma cytokines suppressed expression of profibrotic genes, reduced amount of α-smooth muscle actin filaments and decreased contraction of cardiac fibroblasts. In this study, we provided a proof-of-concept that heart non-specific Teff cells could effectively contribute to myocarditis and protect the heart from the dilated cardiomyopathy outcome.",
keywords = "Animals, Autoimmune Diseases/immunology, CD4-Positive T-Lymphocytes/physiology, Fibrosis/immunology, Humans, Mice, Myocarditis/immunology, Myocardium/immunology",
author = "Martina Zarak-Crnkovic and Gabriela Kania and Agnieszka Ja{\'z}wa-Kusior and Marcin Czepiel and Wijnen, {Winandus J} and Jaros{\l}aw Czy{\.z} and Bj{\"o}rn M{\"u}ller-Edenborn and Daria Vdovenko and Diana Lindner and Cristina Gil-Cruz and Marta Bachmann and Dirk Westermann and Burkhard Ludewig and Oliver Distler and L{\"u}scher, {Thomas F} and Karin Klingel and Urs Eriksson and Przemys{\l}aw B{\l}yszczuk",
year = "2019",
month = dec,
day = "20",
doi = "10.1007/s00395-019-0766-6",
language = "English",
volume = "115",
pages = "6",
journal = "BASIC RES CARDIOL",
issn = "0300-8428",
publisher = "D. Steinkopff-Verlag",
number = "1",

}

RIS

TY - JOUR

T1 - Heart non-specific effector CD4+ T cells protect from postinflammatory fibrosis and cardiac dysfunction in experimental autoimmune myocarditis

AU - Zarak-Crnkovic, Martina

AU - Kania, Gabriela

AU - Jaźwa-Kusior, Agnieszka

AU - Czepiel, Marcin

AU - Wijnen, Winandus J

AU - Czyż, Jarosław

AU - Müller-Edenborn, Björn

AU - Vdovenko, Daria

AU - Lindner, Diana

AU - Gil-Cruz, Cristina

AU - Bachmann, Marta

AU - Westermann, Dirk

AU - Ludewig, Burkhard

AU - Distler, Oliver

AU - Lüscher, Thomas F

AU - Klingel, Karin

AU - Eriksson, Urs

AU - Błyszczuk, Przemysław

PY - 2019/12/20

Y1 - 2019/12/20

N2 - Heart-specific CD4+ T cells have been implicated in development and progression of myocarditis in mice and in humans. Here, using mouse models of experimental autoimmune myocarditis (EAM) we investigated the role of heart non-specific CD4+ T cells in the progression of the disease. Heart non-specific CD4+ T cells were obtained from DO11.10 mice expressing transgenic T cell receptor recognizing chicken ovalbumin. We found that heart infiltrating CD4+ T cells expressed exclusively effector (Teff) phenotype in the EAM model and in hearts of patients with lymphocytic myocarditis. Adoptive transfer experiments showed that while heart-specific Teff infiltrated the heart shortly after injection, heart non-specific Teff effectively accumulated during myocarditis and became the major heart-infiltrating CD4+ T cell subset at later stage. Restimulation of co-cultured heart-specific and heart non-specific CD4+ T cells with alpha-myosin heavy chain antigen showed mainly Th1/Th17 response for heart-specific Teff and up-regulation of a distinct set of extracellular signalling molecules in heart non-specific Teff. Adoptive transfer of heart non-specific Teff in mice with myocarditis did not affect inflammation severity at the peak of disease, but protected the heart from adverse post-inflammatory fibrotic remodelling and cardiac dysfunction at later stages of disease. Furthermore, mouse and human Teff stimulated in vitro with common gamma cytokines suppressed expression of profibrotic genes, reduced amount of α-smooth muscle actin filaments and decreased contraction of cardiac fibroblasts. In this study, we provided a proof-of-concept that heart non-specific Teff cells could effectively contribute to myocarditis and protect the heart from the dilated cardiomyopathy outcome.

AB - Heart-specific CD4+ T cells have been implicated in development and progression of myocarditis in mice and in humans. Here, using mouse models of experimental autoimmune myocarditis (EAM) we investigated the role of heart non-specific CD4+ T cells in the progression of the disease. Heart non-specific CD4+ T cells were obtained from DO11.10 mice expressing transgenic T cell receptor recognizing chicken ovalbumin. We found that heart infiltrating CD4+ T cells expressed exclusively effector (Teff) phenotype in the EAM model and in hearts of patients with lymphocytic myocarditis. Adoptive transfer experiments showed that while heart-specific Teff infiltrated the heart shortly after injection, heart non-specific Teff effectively accumulated during myocarditis and became the major heart-infiltrating CD4+ T cell subset at later stage. Restimulation of co-cultured heart-specific and heart non-specific CD4+ T cells with alpha-myosin heavy chain antigen showed mainly Th1/Th17 response for heart-specific Teff and up-regulation of a distinct set of extracellular signalling molecules in heart non-specific Teff. Adoptive transfer of heart non-specific Teff in mice with myocarditis did not affect inflammation severity at the peak of disease, but protected the heart from adverse post-inflammatory fibrotic remodelling and cardiac dysfunction at later stages of disease. Furthermore, mouse and human Teff stimulated in vitro with common gamma cytokines suppressed expression of profibrotic genes, reduced amount of α-smooth muscle actin filaments and decreased contraction of cardiac fibroblasts. In this study, we provided a proof-of-concept that heart non-specific Teff cells could effectively contribute to myocarditis and protect the heart from the dilated cardiomyopathy outcome.

KW - Animals

KW - Autoimmune Diseases/immunology

KW - CD4-Positive T-Lymphocytes/physiology

KW - Fibrosis/immunology

KW - Humans

KW - Mice

KW - Myocarditis/immunology

KW - Myocardium/immunology

U2 - 10.1007/s00395-019-0766-6

DO - 10.1007/s00395-019-0766-6

M3 - SCORING: Journal article

C2 - 31863205

VL - 115

SP - 6

JO - BASIC RES CARDIOL

JF - BASIC RES CARDIOL

SN - 0300-8428

IS - 1

ER -