Dysregulated CD4+ T Cells and microRNAs in Myocarditis

Wang, Jing; Han, Bo

doi:10.3389/fimmu.2020.00539

Cited by 33 publications

(35 citation statements)

References 165 publications

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“…CD4 + T cells are key pathogenic players underlying the development and progression of myocarditis, and the effector subsets promote autoimmune responses [ 22 ]. Therefore, we next assessed the CD4 + T-cell function of rBCG-MyHCα-immunized mice.…”

Section: Resultsmentioning

confidence: 99%

A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette–Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

Tajiri

Imanaka‐Yoshida

Tsujimura

et al. 2021

IJMS

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Dilated cardiomyopathy (DCM) is a potentially lethal disorder characterized by progressive impairment of cardiac function. Chronic myocarditis has long been hypothesized to be one of the causes of DCM. However, owing to the lack of suitable animal models of chronic myocarditis, its pathophysiology remains unclear. Here, we report a novel mouse model of chronic myocarditis induced by recombinant bacille Calmette-Guérin (rBCG) expressing a CD4+ T-cell epitope of cardiac myosin heavy chain-α (rBCG-MyHCα). Mice immunized with rBCG-MyHCα developed chronic myocarditis, and echocardiography revealed dilation and impaired contraction of ventricles, similar to those observed in human DCM. In the heart, CD62L−CD4+ T cells were increased and produced significant amounts of IFN-γ and IL-17 in response to cardiac myosin. Adoptive transfer of CD62L−CD4+ T cells induced myocarditis in the recipient mice, which indicated that CD62L−CD4+ T cells were the effector cells in this model. rBCG-MyHCα-infected dendritic cells produced proinflammatory cytokines and induced MyHCα-specific T-cell proliferation and Th1 and Th17 polarization. This novel chronic myocarditis mouse model may allow the identification of the central pathophysiological and immunological processes involved in the progression to DCM.

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Section: Resultsmentioning

confidence: 99%

A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette–Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

Tajiri

Imanaka‐Yoshida

Tsujimura

et al. 2021

IJMS

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show abstract

“…132 These are classified into myomiRs, and those related to cardiotropic virus infections, immune status, and fibrosis. 132 Since miRNAs can epigenetically regulate cardiac functions, their ablations can lead to developmental defects in the cardiovascular system and also alter immune functions. 133,134 For example, deficiency of miR155 led to attenuated CVB3 myocarditis occurring in association with reduced CD45 + infiltrations in hearts with an immune response skewed toward Th2 and M2 polarizations, suggesting that miR155 has a prominent role in disease induction with CVB3.…”

Section: Other Knockout Modelsmentioning

confidence: 99%

Section: Cvb3‐induced Myocarditis In the Mousementioning

confidence: 99%

“…It has been recently appreciated that miRNAs have a role in the development of myocarditis based on the detection of dysregulated intracellular miRNAs in heart biopsies in patients with myocarditis and DCM 132 . These are classified into myomiRs, and those related to cardiotropic virus infections, immune status, and fibrosis 132 . Since miRNAs can epigenetically regulate cardiac functions, their ablations can lead to developmental defects in the cardiovascular system and also alter immune functions 133,134 .…”

Section: Cvb3‐induced Myocarditis In the Mousementioning

confidence: 99%

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An overview of the immune mechanisms of viral myocarditis

Lasrado

Reddy

2020

Reviews in Medical Virology

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Viral myocarditis has been identified as a major cause of dilated cardiomyopathy (DCM) that can lead to heart failure. Historically, Coxsackieviruses and adenoviruses have been commonly suspected in myocarditis/DCM patients in North America and Europe. However, this notion is changing as other viruses such as Parvovirus B19 and human herpesvirus-6 are increasingly reported as causes of myocarditis in the United States, with the most recent example being the severe acute respiratory syndrome coronavirus 2, causing the Coronavirus Disease-19. The mouse model of Coxsackievirus B3 (CVB3)-induced myocarditis, which may involve mediation of autoimmunity, is routinely used in the study of immune pathogenesis of viral infections as triggers of DCM. In this review, we discuss the immune mechanisms underlying the development of viral myocarditis with an emphasis on autoimmunity in the development of post-infectious myocarditis induced with CVB3.

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“…Infection with the novel pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger myocarditis both directly and indirectly ( 14 , 21 ). Several studies have suggested that the immune response triggered by the virus is the major cause of cardiomyocyte injury, rather than direct virus-mediated cytotoxicity ( 15 , 22 ). In a recent series of hospitalized coronavirus disease 2019 (COVID-19) cases caused by SARS-CoV-2 infection, acute cardiac injury with serum troponin elevation occurred in 7% to 27% of patients, and elevated troponin levels were associated with increased mortality in patients with COVID-19 ( 23 – 25 ).…”

Section: Triggers Of Myocarditismentioning

confidence: 99%

Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy

Tajiri

Yonebayashi

et al. 2021

Front. Immunol.

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Accumulating evidence suggests that the breakdown of immune tolerance plays an important role in the development of myocarditis triggered by cardiotropic microbial infections. Genetic deletion of immune checkpoint molecules that are crucial for maintaining self-tolerance causes spontaneous myocarditis in mice, and cancer treatment with immune checkpoint inhibitors can induce myocarditis in humans. These results suggest that the loss of immune tolerance results in myocarditis. The tissue microenvironment influences the local immune dysregulation in autoimmunity. Recently, tenascin-C (TN-C) has been found to play a role as a local regulator of inflammation through various molecular mechanisms. TN-C is a nonstructural extracellular matrix glycoprotein expressed in the heart during early embryonic development, as well as during tissue injury or active tissue remodeling, in a spatiotemporally restricted manner. In a mouse model of autoimmune myocarditis, TN-C was detectable before inflammatory cell infiltration and myocytolysis became histologically evident; it was strongly expressed during active inflammation and disappeared with healing. TN-C activates dendritic cells to generate pathogenic autoreactive T cells and forms an important link between innate and acquired immunity.

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Dysregulated CD4+ T Cells and microRNAs in Myocarditis

Cited by 33 publications

References 165 publications

A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette–Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette–Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α

An overview of the immune mechanisms of viral myocarditis

Immunomodulatory Role of Tenascin-C in Myocarditis and Inflammatory Cardiomyopathy

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