Mast cells as important regulators in the development of psoriasis

Zhou, Xianliang; Chen, Kun; Zhang, Mengli

doi:10.3389/fimmu.2022.1022986

Cited by 13 publications

(8 citation statements)

References 106 publications

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“…Skin MCs (skMCs) orchestrate innate and adaptive immune responses against intruding pathogens [ 13 , 14 ]. They are also involved in a plethora of chronic inflammatory skin disorders such as atopic and contact dermatitis, psoriasis, rosacea and urticaria, where MCs are overabundant and/or hyperactive [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells

Franke

Bal

et al. 2023

IJMS

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cAMP response element binding protein (CREB) functions as a prototypical stimulus-inducible transcription factor (TF) that initiates multiple cellular changes in response to activation. Despite pronounced expression in mast cells (MCs), CREB function is surprisingly ill-defined in the lineage. Skin MCs (skMCs) are critical effector cells in acute allergic and pseudo-allergic settings, and they contribute to various chronic dermatoses such as urticaria, atopic dermatitis, allergic contact dermatitis, psoriasis, prurigo, rosacea and others. Using MCs of skin origin, we demonstrate herein that CREB is rapidly phosphorylated on serine-133 upon SCF-mediated KIT dimerization. Phosphorylation initiated by the SCF/KIT axis required intrinsic KIT kinase activity and partially depended on ERK1/2, but not on other kinases such as p38, JNK, PI3K or PKA. CREB was constitutively nuclear, where phosphorylation occurred. Interestingly, ERK did not translocate to the nucleus upon SCF activation of skMCs, but a fraction was present in the nucleus at baseline, and phosphorylation was prompted in the cytoplasm and nucleus in situ. CREB was required for SCF-facilitated survival, as demonstrated with the CREB-selective inhibitor 666-15. Knock-down of CREB by RNA interference duplicated CREB’s anti-apoptotic function. On comparison with other modules (PI3K, p38 and MEK/ERK), CREB was equal or more potent at survival promotion. SCF efficiently induces immediate early genes (IEGs) in skMCs (FOS, JUNB and NR4A2). We now demonstrate that CREB is an essential partaker in this induction. Collectively, the ancient TF CREB is a crucial component of skMCs, where it operates as an effector of the SCF/KIT axis, orchestrating IEG induction and lifespan.

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Section: Introductionmentioning

confidence: 99%

CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells

Franke

Bal

et al. 2023

IJMS

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“…In addition, a reduction in the thickness of the skin in the treatment group was seen as measured by HE staining. Mast cells are very important regulators of the development of psoriasis and an increase in infiltrating mast cells exacerbates the development of inflammation [ 31 , 32 ]. We analyzed the effect of TEs on this by toluidine blue staining and found a significant reduction in mast cells in the BT and WT groups compared to the model group.…”

Section: Discussionmentioning

confidence: 99%

Anti-Psoriatic Activity of Black, Green and White Tea Extracts from Southeastern China

Zhang,

Huang,

Xuan

et al. 2024

Molecules

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Psoriasis is a common chronic inflammatory disease, but most of its current treatments come with a high risk of side effects. As one of the world’s top three beverages, tea has a traditional history of being used as a treatment for skin conditions due to its high safety profile, anti-inflammatory and other properties. In this study, we investigated the anti-psoriasis effects of ethanol extracts of black tea, green tea and white tea from southeastern China. The compositions of the tea extracts (TEs) were first determined by UPLC-Q-Exactive-Orbitrap MS and then genetic analysis, antibacterial, anti-inflammatory, and immunocompetence assays were performed. Imiquimod was used to establish a mouse model of psoriasis-like dermatitis and treating with the extracts to examine their efficacy. A total of 88 chemical components, mainly phenols and organic acids, were identified from the TEs. These TEs ameliorated skin damage and they all reduced the expression of cytokines IL-17 and TNF-α. By analyzing the genes, TEs may affect the inflammatory signaling pathway by regulating the metabolic changes. In addition, TEs can significantly scavenge ROS, NO, and inhibit cellular inflammation. In conclusion, this study examined the inhibitory effects of three TEs on psoriasis and their potential as nutritional supplements for the treatment of skin inflammation.

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“…Mast cells are widely present in psoriatic lesions and are overactivated [ 54 ]. Mast cells play a regulatory immune function by releasing a variety of inflammatory mediators and form a complex mast cell-centered immune network with T cells, Tregs, and keratinocytes [ 55 ] In addition, mast cells express two isoforms of SPHK (SPHK1 and SPHK2), which are activated upon FcεRI stimulation and produce higher levels of S1P [ 56 ]. Moreover, mast cells also express S1PRs, in which the activation of S1PR1 promotes mast cell migration toward antigens and the activation of S1PR2 triggers mast cell degranulation.…”

Section: S1p and Its Signaling Affect Psoriasis Pathogenesismentioning

confidence: 99%

Pathogenic sphingosine 1-phosphate pathway in psoriasis: a critical review of its pathogenic significance and potential as a therapeutic target

Zhao

Zhang²,

et al. 2023

Lipids Health Dis

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Sphingosine-1-phosphate (S1P) is a sphingolipid mediator that exerts a variety of biological functions, including immune, cardiovascular, and neurological regulation as well as tumor promotion, through high-affinity G protein-coupled receptors (S1P1-5). It has been reported that circulating S1P levels remain higher in patients with psoriasis than in healthy individuals and that circulating S1P levels do not decrease after anti-TNF-α treatment in those patients. The S1P-S1PR signaling system plays an important role in inhibiting keratinocyte proliferation, regulating lymphocyte migration, and promoting angiogenesis, thus contributing to the regulation of psoriasis pathogenesis. Here, we review the mechanisms by which S1P-S1PR signaling affects the development of psoriasis and the available clinical/preclinical evidence for targeting S1P-S1PR in psoriasis. S1P-S1PR signaling mechanisms may partially explain the link between psoriasis and its comorbidities. Although the detailed mechanisms remain to be elucidated, S1P may be a new target for future psoriasis remission.

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Mast cells as important regulators in the development of psoriasis

Cited by 13 publications

References 106 publications

CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells

CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells

Anti-Psoriatic Activity of Black, Green and White Tea Extracts from Southeastern China

Pathogenic sphingosine 1-phosphate pathway in psoriasis: a critical review of its pathogenic significance and potential as a therapeutic target

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