Elevated IFN-alpha/beta levels in a streptozotocin-induced type I diabetic mouse model promote oxidative stress and mediate depletion of spleen-homing CD8+ T cells by apoptosis through impaired CCL21/CCR7 axis and IL-7/CD127 signaling

Mahmoud, Mohamed H.; Badr, Gamal; Badr, Badr Mohamed; Kassem, Ahmad Usama; Mohamed, Mahmoud Shaaban

doi:10.1016/j.cellsig.2015.07.005

Cited by 8 publications

(3 citation statements)

References 87 publications

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“…To uncover the pathological role of IFN-α in T1D, NOD mice were used as the T1D model and injected with IFN-α. In agreement with previous studies [30], our data showed that IFN-α could accelerate autoimmune insulitis and promoted T cell proliferation and infiltration. The autoreactive T cells interact with MHC complex through T cell receptor (TCR), which perceives MHC signal intensity to regulate T cell proliferation [31].…”

Section: Discussionsupporting

confidence: 93%

Interferon‐α promotes MHC I antigen presentation of islet β cells through STAT1‐IRF7 pathway in type 1 diabetes

Jiang

Shen

et al. 2022

Immunology

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Type 1 diabetes (T1D) is a T cell‐mediated autoimmune disease. Increased incidence of T1D was reported in patients receiving IFN‐α treatment. However, the exact mechanisms of IFN‐α that facilitate the pathogenesis of T1D are not fully understood. To explore the mechanism of IFN‐α on the immune system and islets, non‐obese diabetic (NOD) mice were injected with IFN‐α and the progression of autoimmune insulitis was assessed by haematoxylin and eosin (HE) staining, immunohistochemical and flow cytometry analysis. Transcriptional profiling of islets treated with IFN‐α was explored by RNA‐seq. IFN‐α induced antigen presentation was evaluated by qRT‐PCR, western blot and immunofluorescence, and key transcription factors were inhibited by small interfering RNAs (siRNAs). Our data show that IFN‐α contributed to the progression of autoimmune insulitis in NOD mice by promoting the proliferation of CD8+ T cells. IFN‐α upregulated antigen presentation related genes MHC I, TAP1, B2M, PSMB8, NLRC5 and transcriptional regulator STAT1, STAT2, IRF7 at a time and dose‐dependent manner. The silence of STAT1 or STAT2 both weakened IFN‐α‐induced increase of antigen presenting related molecules. IRF7 was also merely influenced by STAT1 silence. The knockdown of IRF7 decreased the IFN‐α induced expressions of TAP1, PSMB8 and MHC I and prevented the expression of STAT2 but not STAT1. Our study demonstrated that STAT1‐IRF7‐MHC I complex axis were crucial for IFN‐α signalling in islets, and created positive feedback through IRF7‐STAT2 cascade amplifying signals which accelerated the process of T1D.

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Section: Discussionsupporting

confidence: 93%

Interferon‐α promotes MHC I antigen presentation of islet β cells through STAT1‐IRF7 pathway in type 1 diabetes

Jiang

Shen

et al. 2022

Immunology

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“…As a type I IFN, IFN-α functions against infection, neoplasms, and immunity[ 111 ]. IFN-α is involved in the early stage of β cell death in T1D for its autoimmune ability[ 112 ], because IFN-α is markedly increased in the plasma of individuals with T1D, and inhibition of IFN-α/β receptor 1 and antibody against IFN-α can reduce the occurrence of T1D[ 113 , 114 ] (Table 1 ). Additionally, IFN-β is highly expressed in the retina of DR rats[ 115 ] (Table 1 ).…”

Section: Ifn-α In Drmentioning

confidence: 99%

Role of interferons in diabetic retinopathy

Li¹,

Tan²,

Zou³

et al. 2021

WJD

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Diabetic retinopathy (DR) is one of the major causes of visual impairment and irreversible blindness in developed regions. Aside from abnormal angiogenesis, inflammation is the most specific and might be the initiating factor of DR. As a key participant in inflammation, interferon-gamma (IFN-γ) can be detected in different parts of the eye and is responsible for the breakdown of the blood-retina barrier and activation of inflammatory cells and other cytokines, which accelerate neovascularization and neuroglial degeneration. In addition, IFN-γ is involved in other vascular complications of diabetes mellitus and angiogenesis-dependent diseases, such as diabetic nephropathy, cerebral microbleeds, and age-related macular degeneration. Traditional treatments, such as anti-vascular endothelial growth factor agents, vitrectomy, and laser photocoagulation therapy, are more effective for angiogenesis and not tolerable for every patient. Many ongoing clinical trials are exploring effective drugs that target inflammation. For instance, IFN-α acts against viruses and angiogenesis and is commonly used to treat malignant tumors. Moreover, IFN-α has been shown to contribute to alleviating the progression of DR and other ocular diseases. In this review, we emphasize the roles that IFNs play in the pathogenesis of DR and discuss potential clinical applications of IFNs in DR, such as diagnosis, prognosis, and therapeutic treatment.

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“…OVs-mediated tumor destruction is now recognized as a powerful tool to aid the development of anti-tumor immunity ( Glorioso et al., 2021 ). The perfect OV should eliminate cancer cells through a combination of three mechanisms, including the induction of apoptosis, pro-inflammatory cytokines, and interferons ( Schiller et al., 2012 ; Mahmoud et al., 2015 ; Frumence et al., 2016 ). In addition to directly killing tumor cells, OVs activate immune responses or express healing factors to elevate antitumor efficacy, thereby enhancing efficacy of cancer immunotherapies ( Sobhanimonfared et al., 2020 ; Yang et al., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response

Sun²,

Chen

et al. 2023

Front. Cell. Infect. Microbiol.

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Recent reports have revealed that oncolytic viruses (OVs) play a significant role in cancer therapy. The infection of OVs such as oncolytic vaccinia virus (OVV), vesicular stomatitis virus (VSV), parvovirus, mammalian reovirus (MRV), human adenovirus, Newcastle disease virus (NDV), herpes simplex virus (HSV), avian reovirus (ARV), Orf virus (ORFV), inactivated Sendai virus (ISV), enterovirus, and coxsackievirus offer unique opportunities in immunotherapy through diverse and dynamic pathways. This mini-review focuses on the mechanisms of OVs-mediated virotherapy and their effects on immunogenic cell death (ICD), apoptosis, autophagy and regulation of the immune system.

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Elevated IFN-alpha/beta levels in a streptozotocin-induced type I diabetic mouse model promote oxidative stress and mediate depletion of spleen-homing CD8+ T cells by apoptosis through impaired CCL21/CCR7 axis and IL-7/CD127 signaling

Cited by 8 publications

References 87 publications

Interferon‐α promotes MHC I antigen presentation of islet β cells through STAT1‐IRF7 pathway in type 1 diabetes

Interferon‐α promotes MHC I antigen presentation of islet β cells through STAT1‐IRF7 pathway in type 1 diabetes

Role of interferons in diabetic retinopathy

Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response

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