The role of type I IFN in autoimmune and autoinflammatory diseases with CNS involvement

Raftopoulou, Sylvia; Rapti, Anna; Karathanasis, Dimitris; Evangelopoulos, Maria Eleftheria; Mavragani, Clio P.

doi:10.3389/fneur.2022.1026449

Cited by 6 publications

(9 citation statements)

References 123 publications

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“…Elevated type I IFNs signalling has been found in many patients with autoimmune diseases affecting the central nervous system, such as multiple sclerosis, neuropsychiatric lupus erythematosus and AGS. 123 In AGS, whether and how high levels of type I IFNs cause the typical manifestations of AGS including encephalatrophy, cerebral calcification and leukoencephalopathy are largely unknown. Astrocytes were previously identified as a main source of IFN-α in AGS, 124 and chronic exposure of astrocytes to IFN-α results in AGS-related molecular changes.…”

Section: Type I Ifns In Agsmentioning

confidence: 99%

“…126 However, recent study shows that microglia have a more extensive and divergent response to IFN-α compared with astrocytes, 127 and microglia is also the major producing and responding cells of type I IFNs in the central nervous system. 123,128,129 Microglia are resident macrophages in the brain, which play important roles in homeostasis and neurological disorders' pathogenesis. 129 Although type I IFNs may act on various target cells in the brain, in our points of view, a full understanding of the role of chronic type I IFN exposure of microglia in the pathogenesis of AGS is more necessary.…”

Section: Type I Ifns In Agsmentioning

confidence: 99%

“…A variety of clinical and experimental evidence suggests that excessive levels of type I IFNs are toxic to central nervous system, particularly during early neurodevelopment. Elevated type I IFNs signalling has been found in many patients with autoimmune diseases affecting the central nervous system, such as multiple sclerosis, neuropsychiatric lupus erythematosus and AGS 123 . In AGS, whether and how high levels of type I IFNs cause the typical manifestations of AGS including encephalatrophy, cerebral calcification and leukoencephalopathy are largely unknown.…”

Section: Ags Is the Prototype Of Type I Interferonopathiesmentioning

confidence: 99%

“…Therefore, astrocytes were regarded as an active player in AGS 126 . However, recent study shows that microglia have a more extensive and divergent response to IFN‐α compared with astrocytes, 127 and microglia is also the major producing and responding cells of type I IFNs in the central nervous system 123,128,129 . Microglia are resident macrophages in the brain, which play important roles in homeostasis and neurological disorders' pathogenesis 129 .…”

Section: Ags Is the Prototype Of Type I Interferonopathiesmentioning

confidence: 99%

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Aicardi–Goutières syndrome: A monogenic type I interferonopathy

Liu

Shi

2023

Scand J Immunol

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Aicardi–Goutières syndrome (AGS) is a rare monogenic autoimmune disease that primarily affects the brains of children patients. Its main clinical features include encephalatrophy, basal ganglia calcification, leukoencephalopathy, lymphocytosis and increased interferon‐α (IFN‐α) levels in the patient's cerebrospinal fluid (CSF) and serum. AGS may be caused by mutations in any one of nine genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1, LSM11 and RNU7‐1) that result in accumulation of self‐nucleic acids in the cytoplasm or aberrant sensing of self‐nucleic acids. This triggers overproduction of type I interferons (IFNs) and subsequently causes AGS, the prototype of type I interferonopathies. This review describes the discovery history of AGS with various genotypes and provides the latest knowledge of clinical manifestations and causative genes of AGS. The relationship between AGS and type I interferonopathy and potential therapeutic methods for AGS are also discussed in this review.

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Section: Type I Ifns In Agsmentioning

confidence: 99%

Section: Type I Ifns In Agsmentioning

confidence: 99%

Section: Ags Is the Prototype Of Type I Interferonopathiesmentioning

confidence: 99%

Section: Ags Is the Prototype Of Type I Interferonopathiesmentioning

confidence: 99%

See 2 more Smart Citations

Aicardi–Goutières syndrome: A monogenic type I interferonopathy

Liu

Shi

2023

Scand J Immunol

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“…Autoinflammatory monogenic disorders characterised by high levels of IL-1β are well recognised and are termed “inflammasomopathies,” such as cryopyrin-associated periodic syndromes consisting of gain-of-function mutations of NLRP3 ( Voet et al, 2019 ; Alehashemi & Goldbach-Mansky, 2020 ; Krainer et al, 2020 ). Mutations in several genes of the IFN signalling pathway lead to a spectrum of diseases known as “type I interferonopathies,” which result in unregulated production of type I IFN and ISGs ( Crow & Stetson, 2022 ) and which are characterised by multiple symptoms of systemic inflammation ( Raftopoulou et al, 2022 ). Among the syndromes recognised as type I interferonopathies are Aicardi–Goutières syndrome, spondyloenchondrodysplasia, or STING-associated vasculopathy.…”

Section: Introductionmentioning

confidence: 99%

Type I interferon regulates interleukin-1beta and IL-18 production and secretion in human macrophages

Díaz-Pino,

Rice,

San Felipe

et al. 2024

Life Sci. Alliance

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Inflammasomes are immune complexes whose activation leads to the release of pro-inflammatory cytokines IL-18 and IL-1β. Type I IFNs play a role in fighting infection and stimulate the expression of IFN-stimulated genes (ISGs) involved in inflammation. Despite the importance of these cytokines in inflammation, the regulation of inflammasomes by type I IFNs remains poorly understood. Here, we analysed RNA-sequencing data from patients with monogenic interferonopathies and found an up-regulation of several inflammasome-related genes. To investigate the effect of type I IFN on the inflammasome, we treated human monocyte-derived macrophages with IFN-α and observed an increase inCASP1andGSDMDmRNA levels over time, whereasIL1BandNLRP3were not directly correlated to IFN-α exposure time. IFN-α treatment reduced the release of mature IL-1β and IL-18, but not caspase-1, in response to ATP-mediated NLRP3 inflammasome activation, suggesting regulation occurs at cytokine expression levels and not the inflammasome itself. However, more studies are required to investigate how regulation by IFN-α occurs and impacts NLRP3 and other inflammasomes at both transcriptional and post-translational levels.

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Varicella‐zoster virus‐related neurological complications: From infection to immunomodulatory therapies

Hakami,

Khan,

Abdulaziz

et al. 2024

Reviews in Medical Virology

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The Varicella‐zoster virus (VZV), classified as a neurotropic member of the Herpesviridae family, exhibits a characteristic pathogenicity, predominantly inducing varicella, commonly known as chickenpox, during the initial infectious phase, and triggering the reactivation of herpes zoster, more commonly recognized as shingles, following its emergence from a latent state. The pathogenesis of VZV‐associated neuroinflammation involves a complex interplay between viral replication within sensory ganglia and immune‐mediated responses that contribute to tissue damage and dysfunction. Upon primary infection, VZV gains access to sensory ganglia, establishing latent infection within neurons. During reactivation, the virus can spread along sensory nerves, triggering a cascade of inflammatory mediators, chemokines, and immune cell infiltration in the affected neural tissues. The role of both adaptive and innate immune reactions, including the contributions of T and B cells, macrophages, and dendritic cells, in orchestrating the immune‐mediated damage in the central nervous system is elucidated. Furthermore, the aberrant activation of the natural defence mechanism, characterised by the dysregulated production of immunomodulatory proteins and chemokines, has been implicated in the pathogenesis of VZV‐induced neurological disorders, such as encephalitis, myelitis, and vasculopathy. The intricate balance between protective and detrimental immune responses in the context of VZV infection emphasises the necessity for an exhaustive comprehension of the immunopathogenic mechanisms propelling neuroinflammatory processes. Despite the availability of vaccines and antiviral therapies, VZV‐related neurological complications remain a significant concern, particularly in immunocompromised individuals and the elderly. Elucidating these mechanisms might facilitate the emergence of innovative immunomodulatory strategies and targeted therapies aimed at mitigating VZV‐induced neuroinflammatory damage and improving clinical outcomes. This comprehensive understanding enhances our grasp of viral pathogenesis and holds promise for pioneering therapeutic strategies designed to mitigate the neurological ramifications of VZV infections.

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The role of type I IFN in autoimmune and autoinflammatory diseases with CNS involvement

Cited by 6 publications

References 123 publications

Aicardi–Goutières syndrome: A monogenic type I interferonopathy

Aicardi–Goutières syndrome: A monogenic type I interferonopathy

Type I interferon regulates interleukin-1beta and IL-18 production and secretion in human macrophages

Varicella‐zoster virus‐related neurological complications: From infection to immunomodulatory therapies

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