Mitochondrial Reactive Oxygen Species Are Essential for the Development of Psoriatic Inflammation

Abstract

Psoriasis is a common immune-mediated, chronic, inflammatory skin disease that affects approximately 2–3% of the population worldwide. Although there is increasing evidence regarding the essential roles of the interleukin (IL)-23/IL-17 axis and dendritic cell (DC)-T cell crosstalk in the development of skin inflammation, the contributions of mitochondrial function to psoriasis are unclear. In a mouse model of imiquimod (IMQ)-induced psoriasiform skin inflammation, we found that hematopoietic cell-specific genetic deletion of p32/C1qbp, a regulator of mitochondrial protein synthesis and metabolism, protects mice from IMQ-induced psoriatic inflammation. Additionally, we demonstrate that p32/C1qbp is an important regulator of IMQ-induced DC activation, both in vivo and in vitro. We also found that p32/C1qbp-deficient DCs exhibited impaired production of IL-1β, IL-23, and mitochondrial reactive oxygen species (mtROS) after IMQ stimulation. Because the inhibition of mtROS suppressed IMQ-induced DC activation and psoriatic inflammation, we presume that p32/C1qbp and mtROS can serve as therapeutic targets in psoriasis.

Oxidative Stress and Gut Microbiome in Inflammatory Skin Diseases

“…The result accentuated the unfolded protein response (UPR) and induced the production of IL-23. Mizuguchi et al also showed that mtROS-dependent IL-1β is involved in exacerbating psoriatic inflammation( Mizuguchi et al, 2021 ).…”

Attenuating Effect of Chlorella Extract on NLRP3 Inflammasome Activation by Mitochondrial Reactive Oxygen Species

“…For direct immunoblotting, pMACs and BMDMs were lysed with cell lysis buffer (Cell Signaling Technology) as described (25). The lysate was eluted with sample buffer and boiled for 5 min at 97 • C. SDS-PAGE was performed with 8-15% polyacrylamide gels.…”

“…For mtROS measurement using MitoSOX as described (25), macrophages were incubated with ATP or nigericin and treated MitoSOX (5 µM, Thermo Fisher Scientific, #M36008) last 10 min, in accordance with the manufacturer's instructions. The supernatant was removed and resuspended in HBSS.…”

Complement C1q Binding Protein (C1QBP): Physiological Functions, Mutation-Associated Mitochondrial Cardiomyopathy and Current Disease Models

“…C1QBP is reported to exert pleiotropic effects on many cellular processes, including mitochondrial homeostasis, mitochondrial oxidative phosphorylation (OXPHOS) and in nucleus-mitochondrial interactions, inflammation, and cancer (15)(16)(17)(18)(19). Biallelic C1QBP mutations were recently identified manifesting as combined oxidative phosphorylation deficiency (COXPD) in an autosomal recessive inherited pattern.…”

“…Disease-associated mutations of C1QBP in mitochondrial disease.Frontiers in Cardiovascular Medicine | www.frontiersin.org vasoactive peptide bradykinin largely responsible for the swelling seen in angioedema(17)(18)(19).…”