Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis

Zhan, Hongbing; Hua, Xiumeng; Mo, Xiuxue; Chen, Yuan; Chen, Xiao; Xu, Zhenyu; Tao, Mengtao; Hu, Gang; Song, Jiangping

doi:10.1016/j.isci.2023.107162

Cited by 6 publications

(4 citation statements)

References 74 publications

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“…Single-cell RNA-Seq data preprocessing and clustering with DESC was performed according to previously method 32 . Briefly, single-cell RNA-seq data were pre-processed and qualitied with Seurat (version 4) 33 .…”

Section: Methodsmentioning

confidence: 99%

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons

Gao,

Shi,

Wei

et al. 2024

Int. J. Biol. Sci.

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Peristaltic movements in gut are essential to propel ingested materials through the gastrointestinal tract. Intestinal resident macrophages play an important role in this physiological function through protecting enteric neurons. However, it is incompletely clear how individuals maintain the homeostasis of gut motility. Here we found that NLRP3 is a critical factor in controlling loss of muscularis resident macrophages (MMs), and demonstrate that MMs are involved in the homeostasis of excitatory neurons such as choline acetyltransferase (ChAT) + and vesicular glutamate transporter 2 (VGLUT2) + but not inhibitory neuronal nitric oxide synthase (nNOS) + neurons. NLRP3 knockout (KO) mice had enhanced gut motility and increased neurons, especially excitatory ChAT + and VGLUT2 + neurons. Single cell analyses showed that there had increased resident macrophages, especially MMs in NLRP3 KO mice. The MM proportion in the resident macrophages was markedly higher than those in wild-type (WT) or caspase 1/11 KO mice. Deletion of the MMs and transplantation of the NLRP3 KO bone marrow cells showed that survival of the gut excitatory ChAT + and VGLUT2 + neurons was dependent on the MMs. Gut microbiota metabolites β-hydroxybutyrate (BHB) could promote gut motility through protecting MMs from pyroptosis. Thus, our data suggest that MMs regulated by NLRP3 maintain the homeostasis of excitatory neurons.

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Section: Methodsmentioning

confidence: 99%

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons

Gao,

Shi,

Wei

et al. 2024

Int. J. Biol. Sci.

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“…In addition, a single-cell analysis approach revealed that a majority of cardiac infiltrating T cells are CD4 + T cells expressing Il17a and Il22 in this model. 193 However, despite the disease phenotype, the transfer of antibodies from these immunized rats did not elicit myocarditis in recipient rats, suggesting that further studies are required to fully understand the role of autoantibodies in giant cell myocarditis. 57 Unlike antibodies, the adoptive transfer of T cells isolated from the immunized rats successfully induced myocarditis in recipients, indicating that autoreactive T cells targeting heart antigens may play a crucial role in giant cell myocarditis.…”

Section: Autoimmune Mechanisms In Different Types Of Myocarditismentioning

confidence: 97%

“…56,[110][111][112][113] RNA sequencing studies using single-cell technology revealed that macrophages, with heterogeneous origins, constituted the largest immune cell population in giant cell myocarditis, and multinucleated giant cells might originate from a particular macrophage subset expressing transmembrane GPNMB (glycoprotein NMB). 193,194 Additionally, there is evidence suggesting a pathogenic role of neutrophils through the formation of neutrophil extracellular traps in giant cell myocarditis, as tested using mouse models and heart tissue samples from patients. 193…”

Section: Giant Cell Myocarditismentioning

confidence: 99%

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Autoimmune Myocarditis, Old Dogs and New Tricks

Won,

Song,

Kalinoski

et al. 2024

Circulation Research

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Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.

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New insights gained from cellular landscape changes in myocarditis and inflammatory cardiomyopathy

Wang,

Jia,

Hua

et al. 2024

Heart Fail Rev

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Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis

Cited by 6 publications

References 74 publications

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons

Muscularis macrophages controlled by NLRP3 maintain the homeostasis of excitatory neurons

Autoimmune Myocarditis, Old Dogs and New Tricks

New insights gained from cellular landscape changes in myocarditis and inflammatory cardiomyopathy

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