IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis

Hou, Yuzhu; Zhu, Linnan; Tian, Hua; Sun, Hai‐Xi; Wang, Ruoyu; Zhang, Lianfeng; Zhao, Yong

doi:10.1007/s13238-018-0505-z

Cited by 105 publications

(82 citation statements)

References 46 publications

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“…It has been proved that IMQ-induced psoriasis-like skin inflammation is a typical disease associated with IL-23/IL-17 axis imbalance ( 54 , 55 ). Upregulated IL-23 and IL-17 have been found in both psoriatic patients ( 56 ) and psoriasis-like mice ( 57 ). IL-23 activates Th17 cells through STAT3 pathway, thus producing Th17-related cytokines, such as IL-17, IL-22, and TNF-α ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Esculetin Ameliorates Psoriasis-Like Skin Disease in Mice by Inducing CD4+Foxp3+ Regulatory T Cells

et al. 2018

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Psoriasis is an autoimmune and inflammatory skin disease affecting around 2–3% of the world's population. Patients with psoriasis need extensive treatments with global immunosuppressive agents that may cause severe side effects. Esculetin, a type of coumarins, is an active ingredient extracted mainly from the bark of Fraxinus rhynchophylla, which has been used to treat inflammatory and autoimmune diseases in China. However, the antipsoriatic effects of esculetin have not been reported. In this study, we aimed to investigate the effects of esculetin on psoriatic skin inflammation in a mouse model and explored the potential molecular mechanisms underlying its action. We found that esculetin ameliorated the skin lesion and reduced PASI scores as well as weight loss in imiquimod-induced psoriasis-like mice, accompanied with weakened proliferation and differentiation of keratinocytes and T cell infiltration in esculetin-treated psoriatic mice. In addition, esculetin reduced the frequency of CD8+CD44highCD62Llow effector T cells in psoriatic mice. In contrast, it increased the frequency of CD4+Foxp3+ Tregs in both lymph nodes and spleens of the psoriatic mice while promoting the differentiation of CD4+CD25− T cells into CD4+Foxp3+ Tregs in vitro. Interestingly, depleting CD4+Foxp3+ Tregs largely reversed esculetin-mediated reduction in PASI scores, indicating that esculetin attenuates murine psoriasis mainly by inducing CD4+Foxp3+ Tregs. Furthermore, the mRNA levels of proinflammatory cytokines in the psoriatic mouse skin, including IL-6, IL-17A, IL-22, IL-23, TNF-α, and IFN-γ, were dramatically decreased by the treatment with esculetin. Finally, we found that esculetin inhibited the phosphorylation of IKKα and P65 in the psoriatic skin, suggesting that it inhibits the activation of NF-κB signaling. Thus, we have demonstrated that esculetin attenuates psoriasis-like skin lesion in mice and may be a potential therapeutic candidate for the treatment of psoriasis in clinic.

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Section: Discussionmentioning

confidence: 99%

Esculetin Ameliorates Psoriasis-Like Skin Disease in Mice by Inducing CD4+Foxp3+ Regulatory T Cells

et al. 2018

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“…After the differentiation of macrophages from HPCs under modeled microgravity or normal gravity conditions, we applied either IFN-γ and LPS or IL-4 to stimulate M1 and M2 polarization, respectively, as reported previously. 25,26 The results showed that both M1 and M2 polarization were significantly impaired in macrophages that were differentiated under modeled microgravity (Fig. 2).…”

Section: Spaceflight and Simulated Microgravity Significantly Inhibitmentioning

confidence: 93%

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

et al. 2020

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Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.

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“…Alternatively, CD163+ macrophages were also shown to harbor this effector function. However, the in vivo distinction of a rather DC-like state versus a macrophage-like state is nontrivial, and the role of Tip-DCs/macrophages is under debate [70,71]. Although a single prominent cell type might be responsible for a certain cytokine response in a specific disease state, the cytokine milieu is sustained by various contributors (e.g., Langerhans cells, inflammatory dendritic cells, and mast cells [72][73][74]).…”

Section: Psoriasismentioning

confidence: 99%

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

Schwingen

Kaplan

Kurschus

2020

IJMS

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During the last decades, high-throughput assessment of gene expression in patient tissues using microarray technology or RNA-Seq took center stage in clinical research. Insights into the diversity and frequency of transcripts in healthy and diseased conditions provide valuable information on the cellular status in the respective tissues. Growing with the technique, the bioinformatic analysis toolkit reveals biologically relevant pathways which assist in understanding basic pathophysiological mechanisms. Conventional classification systems of inflammatory skin diseases rely on descriptive assessments by pathologists. In contrast to this, molecular profiling may uncover previously unknown disease classifying features. Thereby, treatments and prognostics of patients may be improved. Furthermore, disease models in basic research in comparison to the human disease can be directly validated. The aim of this article is not only to provide the reader with information on the opportunities of these techniques, but to outline potential pitfalls and technical limitations as well. Major published findings are briefly discussed to provide a broad overview on the current findings in transcriptomics in inflammatory skin diseases.

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IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis

Cited by 105 publications

References 46 publications

Esculetin Ameliorates Psoriasis-Like Skin Disease in Mice by Inducing CD4+Foxp3+ Regulatory T Cells

Esculetin Ameliorates Psoriasis-Like Skin Disease in Mice by Inducing CD4+Foxp3+ Regulatory T Cells

Spaceflight and simulated microgravity suppresses macrophage development via altered RAS/ERK/NFκB and metabolic pathways

Review—Current Concepts in Inflammatory Skin Diseases Evolved by Transcriptome Analysis: In-Depth Analysis of Atopic Dermatitis and Psoriasis

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