Ferroptosis and Autoimmune Diseases

Lai, Benjamin; Wu, Chien‐Hsiang; Wu, Chao‐Yi; Luo, Shue‐Fen; Lai, Jenn‐Haung

doi:10.3389/fimmu.2022.916664

Cited by 44 publications

(27 citation statements)

References 110 publications

(166 reference statements)

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“…For example, Talaromyces marneffei can activate pyroptosis mediated by AIM2-caspase-1/-4-GSDMD in hepatocytes [99]. Moreover, some researchers have begun to pay attention to pyroptosis and ferroptosis in autoimmune diseases and drugs toxicity [100][101][102][103][104]. Our results provide pyroptosis/ ferroptosis-associated signatures in several autoimmune diseases at the single-cell level, which provide extremely precise target information for the application of novel therapeutic approaches.…”

Section: Discussionmentioning

confidence: 76%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

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Background Approximately 8–9% of the world’s population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. Methods Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. Results A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. Conclusion These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

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Section: Discussionmentioning

confidence: 76%

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Zhang

et al. 2022

J Transl Med

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“…Ferroptosis is involved in several pathophysiological processes and the development of miscellaneous conditions, including iron overload disease and myocardial diseases ( Yang et al, 2020 ; Liu and Gu, 2021 ; Weber et al, 2021 ; Lai et al, 2022 ; Liu and Gu, 2022 ). Reasonable induction or inhibition of ferroptosis contributes to the treatment of these diseases.…”

Section: Ferroptosis Inhibitors In Psoriasis Treatmentmentioning

confidence: 99%

“…Ferroptosis primarily consists of three components: 1) oxidation of PUFAs, 2) excess active iron, and 3) inactivation of GPX4 ( Battaglia et al, 2020 ). Studies have shown that ferroptosis is closely associated with the development of several human diseases, including autoimmune diseases, tumors, infectious diseases, and neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease ( Qiu et al, 2020 ; Reichert et al, 2020 ; Lai et al, 2022 ). The current mini review focused on the mechanisms and treatment of psoriasis associated with ferroptosis and the therapeutic advances that contribute to the effective improvement of psoriatic skin manifestations, including skin thickness and scales, in the role of the inhibition of ferroptosis.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Mechanisms and inhibitors of ferroptosis in psoriasis

Zhou

Yang

et al. 2022

Front. Mol. Biosci.

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Psoriasis is a chronic inflammatory skin disease that features localized or widespread erythema, papules, and scaling. It is common worldwide and may be distributed throughout the whole body. The pathogenesis of psoriasis is quite complex and the result of the interplay of genetic, environmental and immune factors. Ferroptosis is an iron-dependent programmed death that is different from cell senescence, apoptosis, pyroptosis and other forms of cell death. Ferroptosis involves three core metabolites, iron, lipids, and reactive oxygen species (ROS), and it is primarily driven by lipid peroxidation. Ferrostatin-1 (Fer-1) is an effective inhibitor of lipid peroxidation that inhibited the changes related to ferroptosis in erastin-treated keratinocytes and blocked inflammatory responses. Therefore, it has a certain effect on the treatment of psoriatic lesions. Although ferroptosis is closely associated with a variety of human diseases, such as inflammatory diseases, no review has focused on ferroptosis in psoriasis. This mini review primarily focused on the pathogenesis of psoriasis, the mechanisms of ferroptosis, the connection between ferroptosis and psoriasis and ferroptosis inhibitors in psoriasis treatment. We discussed recent research advances and perspectives on the relationship between ferroptosis and psoriasis.

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“…This suggests that NR1D1 can potentially be used as therapeutics in the treatment of patients with RA. Various studies have indicated that ROS could be a new therapeutic target for RA treatment regarding ferroptosis ( Xie et al, 2016 ; Xie et al, 2021 ; Chang et al, 2022 ; Lai et al, 2022 ).…”

Section: Use Of Ferroptosis-related Drugs In Rheumatoid Arthritis Tre...mentioning

confidence: 99%

Advancement in understanding the role of ferroptosis in rheumatoid arthritis

et al. 2022

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Rheumatoid arthritis (RA) is a chronic, systemic disease of unknown etiology. The primary manifestation of RA is inflammatory synovitis, which eventually leads to deformity and functional loss. Ferroptosis is a non-apoptosis form of cell death that depends on intracellular iron accumulation. This leads to an increase in reactive oxygen species (ROS) induced-lipid peroxidation. The underlying mechanisms of ferroptosis are System Xc- and Glutathione metabolism, regulation of glutathione peroxidase 4 activity, and ROS generation. Recent studies have shown an association between the pathogenesis of RA and ferroptosis, suggesting the involvement of ferroptosis in the onset and progression of RA. In this review, we have focused on the mechanism of ferroptosis and its association with RA pathogenesis. Further, we discuss the status of therapeutics targeting ferroptosis in the treatment of patients with RA. Targeting ferroptosis could be a potential therapeutic approach for RA treatment.

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Ferroptosis and Autoimmune Diseases

Cited by 44 publications

References 110 publications

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Evidence of pyroptosis and ferroptosis extensively involved in autoimmune diseases at the single-cell transcriptome level

Mechanisms and inhibitors of ferroptosis in psoriasis

Advancement in understanding the role of ferroptosis in rheumatoid arthritis

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