New insight in treating autoimmune diseases by targeting autophagy

Lyu, Jiao; Zhang, Hongqian; Wang, Chaoyang; Pan, Mingyu

doi:10.1080/08916934.2024.2351872

Autoimmunity

2024

DOI: 10.1080/08916934.2024.2351872

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New insight in treating autoimmune diseases by targeting autophagy

Jiao Lyu,

Hongqian Zhang,

Chaoyang Wang

et al.

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2024

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Cited by 2 publications

References 200 publications

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Cordycepin ameliorates autoimmunity by promoting STING degradation via autophagy pathway

Yang,

Peng,

Zhang

et al. 2024

British J Pharmacology

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Background and PurposeStimulator of interferon response cGAMP interactor 1 (STING), a central hub protein of cyclic GMP‐AMP synthase (cGAS)–STING signalling pathway, has a crucial role in regulating type I interferons (IFNs) production and response. Recent studies indicate that excessive activation of STING is strongly associated with autoimmune diseases, including systemic lupus erythematosus (SLE). Searching immunomodulators that negatively regulate STING might greatly contribute to the suppression of autoimmunity.Experimental ApproachThe peripheral blood mononuclear cells (PBMCs) of SLE patients, Hela cells, L929 cells and bone marrow‐derived macrophages (BMDMs) from mice were used as in vitro models. While, Trex1 KO mouse autoimmune disease model was used as in vivo model. After treatment with cordycepin, a nucleoside from Cordyceps mushrooms, type I IFNs production and response were determined by western blotting, real‐time polymerase chain reaction (PCR), dual‐luciferase assay, enzyme‐linked immunosorbent assay (ELISA), haematoxylin–eosin staining and RNA‐seq.Key ResultsCordycepin inhibited type I IFNs production and response in human and murine systems following cGAS–STING signalling activation. Importantly, cordycepin markedly attenuates the autoinflammatory and autoimmune responses in Trex1 KO BMDMs and Trex1 KO mice. Furthermore, cordycepin effectively suppressed the production of type I IFNs and interferon‐stimulated genes (ISGs) in the PBMCs of SLE patients. Mechanistically, cordycepin promoted STING degradation via autophagy pathway upon DNA stimulation.Conclusion and ImplicationsThis study shows that cordycepin promotes STING autophagic degradation to alleviate autoimmunity upon DNA stimulation. Cordycepin might be a potential therapeutic candidate for alleviating aberrant type I IFNs in autoimmune and autoinflammatory diseases.

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Cordycepin ameliorates autoimmunity by promoting STING degradation via autophagy pathway

Yang,

Peng,

Zhang

et al. 2024

British J Pharmacology

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The role of autoantibodies in bridging obesity, aging, and immunosenescence

Valentino,

Chen,

Makhijani

et al. 2024

Immun Ageing

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Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.

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New insight in treating autoimmune diseases by targeting autophagy

Cited by 2 publications

References 200 publications

Cordycepin ameliorates autoimmunity by promoting STING degradation via autophagy pathway

Cordycepin ameliorates autoimmunity by promoting STING degradation via autophagy pathway

The role of autoantibodies in bridging obesity, aging, and immunosenescence

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