Susceptibility to autoimmune myocarditis is associated with intrinsic differences in CD4+ T cells

“…For example, the suppressive activity of peripheral blood Treg (identified as CD4 + CD25 + cells) from Chagas disease was significantly higher if the patients had mild or no cardiomyopathy compared to patients with moderate and severe cardiomyopathy [58]. Comparisons of two MHC identical strains of mice which differ in their susceptibility to EAM have revealed a lower proportion of Treg and higher proportion of T H 17 cells among CD4 + T cells in the susceptible strains compared to the resistant strain [59]. Genetic deficiencies or treatments that result in enhanced myocardial inflammation in the setting of CVB3 infection are also associated with reduced Treg.…”

Section: Regulatory T Cells and Peripheral Tolerance Induction To Trementioning

confidence: 99%

The heart of the matter: Protection of the myocardium from T cells

Lichtman

2013

Journal of Autoimmunity

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Myocardial inflammation and damage can lead to lethal acute or chronic cardiac failure. A variety of regulatory mechanisms limit the magnitude and duration of T cell responses in the heart. Insights into these regulatory mechanisms have come from studies of specific deficiencies in central or peripheral T cell tolerance which cause or enhance the severity of myocarditis. Under non-inflammatory conditions, constitutive DC presentation of cardiac peptides to naïve T cells in cardiac draining lymph nodes tolerizes recirculating naïve T cells specific for these antigens. Cardiac antigen-specific naïve T cells, especially those specific of α-myosin heavy chain peptides, become activated and differentiate into expanded clones of effector T cells under various conditions, such as cardiac infection and/or genetic variations in peripheral tolerance. The pathology that these effector cells cause in the myocardium is limited by PD-L1 expressed on myocardial cells in response to inflammatory cytokines, and by CTLA-4 dependent mechanisms. The PD-1:PD-L1 pathway works together with other pathways to keep the heart safe, a combined genetic deficiencies of PD-1 and other regulatory genes synergize to cause myocarditis. T cell derived IFNγ contributes to the inflammatory damage to the heart in autoimmune myocarditis, but it also engages regulatory mechanisms that limit disease, including upregulation of PD-L1, and differentiation of TNF and iNOS expressing DCs from monocytes. iNOS derived from these DCs and other IFNγ stimulated cells inhibits expansion of T cells that cause myocarditis. Regulatory T cells also appear to be critical for suppression of effector T cells specific for myocardial antigens.

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“…A higher proportion of Treg cells has been shown to be protective against both viral and autoimmune myocarditis in mouse models. Interestingly, further work by Chen et al demonstrated that in autoimmune myocarditis a lower proportion of Treg cells was associated with a greater Th17 response and more severe autoimmune myocarditis [16]. An imbalance between Treg and Th17 cells has recently been observed in idiopathic DCM [12,17].…”

Section: Introductionmentioning

confidence: 99%

Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy

Li¹,

Zhou²,

Tang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. Methods:The levels of plasma RGC-32, IL-17 and TGF-β1, and the frequencies of circulating CD4 + RGC-32 + T cells, Th17 and Treg cells in patients with DCM were determined by Cytokinespecific sandwich ELISA and the flow cytometer (FCM), respectively. Results: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up-or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. Conclusion: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.

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Susceptibility to autoimmune myocarditis is associated with intrinsic differences in CD4+ T cells

Cited by 45 publications

References 43 publications

Cardiac Autoimmunity: Myocarditis

Cardiac Autoimmunity: Myocarditis

The heart of the matter: Protection of the myocardium from T cells

Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy

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