Anti-Peptidylarginine Deiminase 4 Autoantibodies Derived From Patients With Rheumatoid Arthritis Exert Pathogenic Effects by Activating Monocytes and Exacerbating Inflammatory Arthritis.

Objective: Autoantibodies targeting peptidylarginine deiminase 4 (PAD4), an enzyme involved in protein citrullination, are found in a subset of patients with rheumatoid arthritis (RA) with severe joint disease. However, the mechanisms by which anti-PAD4 antibodies participate in disease pathogenesis are incompletely defined.

Methods: We investigated the role of anti-PAD4 monoclonal antibodies derived from patients with RA using a collagen-induced arthritis (CIA) mouse model and human monocyte in vitro cultures.

A membrane lipid signature unravels the dynamic landscape of group 1 innate lymphoid cells across the health-disease continuum.

In an era where established lines between cell identities are blurred by intra-lineage plasticity, distinguishing stable from transitional states is critical, especially within Group 1 ILCs, where similarity and plasticity between NK cells and ILC1s obscure their unique contributions to immunity. This study leverages AsGM1-a membrane lipid associated with cytotoxic attributes absent in ILC1s-as a definitive criterion to discriminate between these cell types. Employing this glycosphingolipid signature, we achieved precise delineation of Group 1 ILC diversity across tissues.

The protective role of GATA6 pericardial macrophages in pericardial inflammation.

Prior research has suggested that GATA6 pericardial macrophages may traffic to the myocardium to prevent interstitial fibrosis after myocardial infarction (MI), while subsequent literature claims that they do not. We demonstrate that GATA6 pericardial macrophages are critical for preventing IL-33 induced pericarditis and attenuate trafficking of inflammatory monocytes and granulocytes to the pericardial cavity after MI. However, absence of GATA6 macrophages did not affect myocardial inflammation due to MI or coxsackievirus-B3 induced myocarditis, or late-stage cardiac fibrosis and cardiac function post MI.

Autoimmune Myocarditis, Old Dogs and New Tricks.

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.

A Membrane Lipid Signature Unravels the Dynamic Landscape of Group 1 ILCs.

In an era where the established lines between cell identities are blurred by intra-lineage plasticity, distinguishing between stable and transitional states becomes imperative. This challenge is particularly pronounced within the Group 1 ILC lineage, where the similarity and plasticity between NK cells and ILC1s obscure their classification and the assignment of their unique contributions to immune regulation. This study exploits the unique property of Asialo-GM1 (AsGM1)-a membrane lipid associated with cytotoxic attributes absent in ILC1s-as a definitive criterion to distinguish between these cells.

Immune checkpoint inhibitors associated cardiovascular immune-related adverse events.

Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene-3 (LAG-3) have improved cancer patient outcomes by enhancing anti-tumor responses. However, some patients are unresponsive, and others experience immune-related adverse events (irAEs), affecting organs like the lung, liver, intestine, skin and now the cardiovascular system.

Programmed Death Ligand 1-Expressing Macrophages and Their Protective Role in the Joint During Arthritis.

Objective: Arthritis associated with immune checkpoint inhibitor therapies highlights the importance of immune checkpoint expression for joint homeostasis. We investigated the role of programmed death ligand (PD-L) 1 in the synovium using a collagen-induced arthritis (CIA) mouse model.

Methods: We blocked PD-L1 using blocking antibodies during CIA and assessed the arthritis severity by clinical and histologic scoring.

Hypereosinophilia causes progressive cardiac pathologies in mice.

Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development.

Integrative single-cell analysis of cardiac and pulmonary sarcoidosis using publicly available cardiac and bronchoalveolar lavage fluid sequencing datasets.

Introduction: Cardiac presentation of autoimmune sarcoidosis, known as cardiac sarcoidosis (CS), is a poorly understood disease with high mortality and low diagnosis rate. While CS is an immunological syndrome, little is known about how cardiac parenchymal and stromal cells mediate its pathogenesis. Moreover, while most current sarcoidosis research is based on research in pulmonary sarcoidosis (PS), it remains unclear how much both presentations of sarcoidosis overlap.

Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis.

Immune checkpoint inhibitors (ICIs) are an effective therapy for various cancers; however, they can induce immune-related adverse events (irAEs) as a side effect. Myocarditis is an uncommon, but fatal, irAE caused after ICI treatments. Currently, the mechanism of ICI-associated myocarditis is unclear.

Increased Interleukin 18-Dependent Immune Responses Are Associated With Myopericarditis After COVID-19 mRNA Vaccination.

Myocarditis and myopericarditis may occur after COVID-19 vaccination with an incidence of two to twenty cases per 100,000 individuals, but underlying mechanisms related to disease onset and progression remain unclear. Here, we report a case of myopericarditis following the first dose of the mRNA-1273 COVID-19 vaccine in a young man who had a history of mild COVID-19 three months before vaccination. The patient presented with chest pain, elevated troponin I level, and electrocardiogram abnormality.

Endothelial thrombomodulin downregulation caused by hypoxia contributes to severe infiltration and coagulopathy in COVID-19 patient lungs.

Background: Thromboembolism is a life-threatening manifestation of coronavirus disease 2019 (COVID-19). We investigated a dysfunctional phenotype of vascular endothelial cells in the lungs during COVID-19.

Methods: We obtained the lung specimens from the patients who died of COVID-19.

Endothelial Stromal PD-L1 (Programmed Death Ligand 1) Modulates CD8 T-Cell Infiltration After Heart Transplantation.

Background: The role of checkpoint axes in transplantation has been partially addressed in animal models but not in humans. Occurrence of fulminant myocarditis with allorejection-like immunologic features in patients under anti-PD1 (programmed death cell protein 1) treatment suggests a key role of the PD1/PD-L1 (programmed death ligand 1) axis in cardiac immune homeostasis.

Methods: We cross-sectionally studied 23 heart transplant patients undergoing surveillance endomyocardial biopsy.

Innate Lymphoid Cells Play a Pathogenic Role in Pericarditis.

We find that cardiac group 2 innate lymphoid cells (ILC2s) are essential for the development of IL-33-induced eosinophilic pericarditis. We show a pathogenic role for ILC2s in cardiac inflammation, in which ILC2s activated by IL-33 drive the development of eosinophilic pericarditis in collaboration with cardiac fibroblasts. ILCs, not T and B cells, are required for the development of pericarditis.

Cutting Edge: Check Your Mice-A Point Mutation in the Locus Identified in CD45.1 Congenic Mice with Consequences in Mouse Susceptibility to Infection.

B6.SJL- /Boy (CD45.1) mice have been used in hundreds of congenic competitive transplants, with the presumption that they differ from C57BL/6 mice only at the CD45 locus.

Isoflavones extracted from Sophorae fructus upregulate IGF-I and TGF-beta and inhibit osteoclastogenesis in rat bone marrow cells.

Isoflavones have been a central subject in research on the natural phytoestrogens found in Leguminosae. Their effects on bone formation and remodeling are important in that they can act like estrogen by binding on estrogen receptors on the target cell surface. We, therefore, believed that isoflavones may help in the treatment of patients with estrogen deficiency disease such as estrogen replacement therapy (ERT) for osteoporosis.

Ursodeoxycholic acid inhibits pro-inflammatory repertoires, IL-1 beta and nitric oxide in rat microglia.

Ursodeoxycholic acid (UDCA) is a non-toxic, hydrophilic bile acid in widespread clinical use mainly for acute and chronic liver disease. Recently, treatment with UDCA in hepatic graft-versus-host disease has been given in immunosuppressive therapy for improvement of the biochemical markers of cholestasis. Moreover, it has been reported that UDCA possesses immunomodulatory effects by the suppression of cytokine production.