Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Sensing by Dendritic Cells in Psoriasis

Lou, Fangzhou; Sun, Yang; Xu, Zhenyao; Niu, Liman; Wang, Zhikai; Deng, Siyu; Liu, Zhaoyuan; Zhou, Hong; Bai, Jing; Yin, Qianqian; Cai, Xiaojie; Sun, Libo; Wang, Hong; Li, Qun; Wu, Zhouwei; Chen, Xiang; Gu, Jun; Shi, Yujun; Tao, Wufan; Ginhoux, Florent

doi:10.1016/j.immuni.2020.06.004

Cited by 90 publications

(62 citation statements)

References 63 publications

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“…IL-17A plays an essential role in inflammation, metabolism, and bone/joint damage (8,10,15,(60)(61)(62). The IL-17 levels and Th17 cell frequencies are high in the skin, synovial fluid, and synovium tissue of the patients with psoriatic arthritis (PsA) (18,(63)(64)(65).…”

Section: Role Of Il-17 Family Members In Psoriasismentioning

confidence: 99%

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

et al. 2020

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Interleukin-17 (IL-17) is an essential proinflammatory cytokine, which is mainly secreted by the CD4 + helper T cells (Th17 cells) and subsets of innate lymphoid cells. IL-17A is associated with the pathogenesis of inflammatory diseases, including psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Interleukin-23 (IL-23) plays a pivotal role in stimulating the production of IL-17 by activating the Th17 cells. The IL-23/IL-17 axis is an important pathway for targeted therapy for inflammatory diseases. Emerging evidence from clinical trials has shown that monoclonal antibodies against IL-23, IL-17, and tumor necrosis factor are effective in the treatment of patients with psoriasis, atopic dermatitis, hidradenitis suppurativa, pityriasis rubra pilaris, pemphigus, and systemic sclerosis. Here, we summarize the latest knowledge about the biology, signaling, and pathophysiological functions of the IL-23/IL-17 axis in inflammatory skin diseases. The currently available biologics targeting the axis is also discussed.

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Section: Role Of Il-17 Family Members In Psoriasismentioning

confidence: 99%

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

et al. 2020

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“…LL37 was reported to form complexes with selfderived RNA as well as self-derived DNA, triggering TLR7 and TLR8 activation in human DCs, which may be associated with psoriasis pathogenesis (221). Another study showed that together with cargo peptides, polyamines form a complex with RNA, promoting endosomal uptake and activation of TLR7 in DCs (222). The decreased expression of protein phosphatase 6 was observed in psoriatic lesions, leading to an increased generation of arginase-1-mediated polyamine.…”

Section: Inflammation Induced By Self-derived Nucleic Acid Recognition In Other Common Diseasesmentioning

confidence: 99%

Signaling Through Nucleic Acid Sensors and Their Roles in Inflammatory Diseases

2021

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Recognition of pathogen-derived nucleic acids by pattern-recognition receptors (PRRs) is essential for eliciting antiviral immune responses by inducing the production of type I interferons (IFNs) and proinflammatory cytokines. Such responses are a prerequisite for mounting innate and pathogen-specific adaptive immune responses. However, host cells also use nucleic acids as carriers of genetic information, and the aberrant recognition of self-nucleic acids by PRRs is associated with the onset of autoimmune or autoinflammatory diseases. In this review, we describe the mechanisms of nucleic acid sensing by PRRs, including Toll-like receptors, RIG-I-like receptors, and DNA sensor molecules, and their signaling pathways as well as the disorders caused by uncontrolled or unnecessary activation of these PRRs.

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“…Conversely, hyperactive arginine metabolism and excessive polyamine production have been observed in psoriasis, an incurable chronic inflammatory disease [132]. Specifically, deficiency in protein phosphatase 6 (PP6) disables skin homeostasis and this has been shown to involve increased ARG1 transcription via phosphorylation and activation of the C/EBP-β transcription factor, and increased production of polyamines.…”

Section: Control Of Polyamine Homeostasis and Interacting Metabolic Pathways In Cancermentioning

confidence: 99%

Polyamine Homeostasis in Development and Disease

Nakanishi

Cleveland

2021

Medical Sciences

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Polycationic polyamines are present in nearly all living organisms and are essential for mammalian cell growth and survival, and for development. These positively charged molecules are involved in a variety of essential biological processes, yet their underlying mechanisms of action are not fully understood. Several studies have shown both beneficial and detrimental effects of polyamines on human health. In cancer, polyamine metabolism is frequently dysregulated, and elevated polyamines have been shown to promote tumor growth and progression, suggesting that targeting polyamines is an attractive strategy for therapeutic intervention. In contrast, polyamines have also been shown to play critical roles in lifespan, cardiac health and in the development and function of the brain. Accordingly, a detailed understanding of mechanisms that control polyamine homeostasis in human health and disease is needed to develop safe and effective strategies for polyamine-targeted therapy.

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Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Sensing by Dendritic Cells in Psoriasis

Cited by 90 publications

References 63 publications

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

The IL-23/IL-17 Pathway in Inflammatory Skin Diseases: From Bench to Bedside

Signaling Through Nucleic Acid Sensors and Their Roles in Inflammatory Diseases

Polyamine Homeostasis in Development and Disease

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