ERK5 is required for neutrophil-mediated ROS release and essential in epidermolysis bullosa acquisita
Draeger, S.; Schlotfeldt, M.; Voss, L.; Johannisson, S.; Radziewitz, M.; Osterloh, C.; Gross, N.; Kamaguchi, M.; Schneider, A.-K.; Vidarsson, G.; Visser, R.; Petersen, F.; Yu, X.; Recke, A.; Ernst, N.; Lux, A.; Bieber, K.
Show abstract
Neutrophils are key effector cells in antibody-mediated autoimmune diseases, contributing to inflammation via the release of reactive oxygen species (ROS). Extracellular signal-regulated kinase 5 (ERK5), a member of the MAPK family, is expressed in neutrophils but its role in autoimmune disease pathogenesis remains unclear. We investigated the functional relevance of ERK5 in antibody-mediated autoimmune diseases by comparing neutrophil-dependent (epidermolysis bullosa acquisita, EBA; serum transfer arthritis, STA) and neutrophil-independent (immune thrombocytopenia, ITP) murine models using the small-molecule ERK5 inhibitor XMD8-92. In vitro, pharmacological ERK5 inhibition specifically reduced neutrophil ROS release and CD62L shedding without affecting adhesion, chemotaxis, or CD18 expression. No major effects on viability were observed. In vivo, ERK5 inhibition with XMD8-92 significantly ameliorated antibody transfer-induced EBA, supporting a critical role of neutrophil-derived ROS in disease pathogenesis. In STA and ITP, ERK5 inhibition did not affect clinical outcomes. Together, these findings highlight ERK5 as a regulator of neutrophil ROS release and a potential therapeutic target in ROS-driven autoimmune diseases such as EBA.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The EGFR/ErbB inhibitor neratinib modifies the neutrophil phosphoproteome and promotes apoptosis and clearance by airway macrophages 93%
- Extrafollicular responses are sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus 93%
- Neutrophils contribute to ER stress in lung epithelial cells in the pristane-induced diffuse alveolar hemorrhage mouse model 93%
Similar papers in this journal
Similar papers in this journal
- FINCA disease mouse model exhibits altered behaviour and immune response 94%
- Extracellular adenosine induces hypersecretion of IL-17A by T-helper 17 cells through the adenosine A2a receptor to promote neutrophilic inflammation 91%
- Thermoregulatory Dynamics Reveal Sex-Specific Inflammatory Responses to Experimental Autoimmune Encephalomyelitis in Mice: Implications for Multiple Sclerosis-Induced Fatigue in Females 91%
Similar papers in this journal
- A Novel human IL-23A Overexpressing Mouse Model of Systemic Lupus Erythematosus 94%
- RNA-Seq analysis identifies novel roles for the primary cilia gene SPAG17 and the SOX9 locus non-coding RNAs in systemic sclerosis 92%
- Loss of TRIM21 drives UVB-induced systemic inflammation by regulating DNA-sensing pathways 91%
Similar papers in this journal
- Beta-adrenergic signaling and T-lymphocyte-produced catecholamines are necessary for interleukin 17A synthesis 93%
- WITHDRAWN: Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model 93%
- Autoimmune inflammation triggers aberrant astrocytic calcium signaling to impair synaptic plasticity 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.