Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

Gong, Xiaoting; Wang, Wei

doi:10.21203/rs.3.rs-63594/v1

Cited by 3 publications

(4 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effectiveness of tumor necrosis factor (TNF)‐α inhibitors in treating psoriasis implies the activation of the innate immune response in psoriasis 2 . Various innate immune cells participate in the pathogenesis of psoriasis, such as macrophages, neutrophils, dendritic cells, γδT cells, and innate lymphoid cells 3 . As vital mediators of the innate immune system, plasmacytoid dendritic cells (pDC) have been confirmed to infiltrate psoriatic lesions 4 …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mannan‐binding lectin exacerbates the severity of psoriasis by promoting plasmacytoid dendritic cell differentiation via the signal transducer and activator of transcription 3–interferon regulatory factor 8 axis

Zeng

Wang

Luo

et al. 2022

The Journal of Dermatology

View full text Add to dashboard Cite

Psoriasis is a chronic inflammatory skin disease mediated by host immune responses. Plasmacytoid dendritic cells (pDC) and interferon (IFN)‐α secreted by pDC are involved in the initiation of psoriasis. Mannan‐binding lectin (MBL), a vital component of the complement pathway, plays a critical role in innate immune defense and the inflammatory response. Our previous study found that MBL could exacerbate skin inflammation in psoriatic mice, but the effect of MBL on pDC remains unstudied. Herein, we revealed that the circulating level of MBL was elevated in patients with psoriasis compared with the healthy controls. Moreover, the MBL level was positively correlated with disease severity, relative inflammatory cytokine levels, and peripheral blood (PB) pDC frequency in psoriasis. An in vitro study determined that the MBL protein could promote the differentiation of human pDC and upregulate the production of relative inflammatory cytokines and chemokines. Additionally, MBL‐deficient (MBL−/−) mice exhibited decreased accumulation of pDC in lymph nodes, spleens, and skin lesions with reduced secretion of pDC‐related cytokines compared with wild‐type (WT) mice in the preliminary stage of psoriasis induced by imiquimod. Notably, the differentiation of pDC from bone marrow (BM) cells derived from MBL−/− mice was weakened compared with that from WT mice upon Fms‐like tyrosine kinase 3 ligand (Flt3L) incubation. Mechanistic research indicated that the signal transducer and activator of transcription 3 (STAT3)–interferon regulatory factor 8 (IRF8) axis was responsible for MBL‐modulated pDC differentiation. In summary, these results suggest that MBL exacerbates the severity of psoriasis by enhancing pDC differentiation and pDC‐related cytokine secretion via the STAT3–IRF8 axis, thus providing a new target for psoriasis treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

“…2 Various innate immune cells participate in the pathogenesis of psoriasis, such as macrophages, neutrophils, dendritic cells, γδT cells, and innate lymphoid cells. 3 As vital mediators of the innate immune system, plasmacytoid dendritic cells (pDC) have been confirmed to infiltrate psoriatic lesions. 4 .…”

Section: Introductionmentioning

confidence: 99%

Mannan‐binding lectin exacerbates the severity of psoriasis by promoting plasmacytoid dendritic cell differentiation via the signal transducer and activator of transcription 3–interferon regulatory factor 8 axis

Zeng

Wang

Luo

et al. 2022

The Journal of Dermatology

View full text Add to dashboard Cite

show abstract

“…These pro-inflammatory molecules promote keratinocyte hyperproliferation and maintain chronic skin inflammation, which are hallmarks of psoriasis [8]. Apart from lymphocytes, monocytes and macrophages also play a role in the pathogenesis of psoriasis [9,10]. The population of monocytes/macrophages was increased in the psoriatic skin lesions, compared to normal skin.…”

Section: Introductionmentioning

confidence: 99%

Signaling pathways and targets of natural products in psoriasis treatment

Nguyen

2022

Exploration of Medicine

View full text Add to dashboard Cite

Aim: Psoriasis is a common chronic inflammatory skin disorder, which has adverse effects on patients’ quality of life. Natural products exhibit significant therapeutic capacities with small side effects and might be preferable alternative treatments for patients with psoriasis. This study summarizes the signaling pathways with the potential targets of natural products and their efficacy for psoriasis treatment. Methods: The literature for this article was acquired from PubMed and Web of Science, from January 2010 to December 2020. The keywords for searching included “psoriasis” and “natural product”, “herbal medicine”, “herbal therapy”, “medicinal plant”, “medicinal herb” or “pharmaceutical plant”. Results: Herbal extracts, natural compounds, and herbal prescriptions could regulate the signaling pathways to alleviate psoriasis symptoms, such as T helper 17 (Th17) differentiation, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), nuclear factor-kappa B (NF-κB), mitogen‑activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and other signaling pathways, which are involved in the inflammatory response and keratinocyte hyperproliferation. The anti-psoriatic effect of natural products in clinical trials was summarized. Conclusions: Natural products exerted the anti-psoriatic effect by targeting multiple signaling pathways, providing evidence for the investigation of novel drugs. Further experimental research should be performed to screen and characterize the therapeutic targets of natural products for application in psoriasis treatment.

show abstract

“…Mast cells (MCs) have been reported to play an irreplaceable role in chronic in ammatory diseases. Studies discovered an increased in ltration of activated MCs and neutrophils in psoriatic lesions, and MCs have been activated in the early stage of the lesions [1][2][3]. MCs are the main source of IL-22 in psoriasis [3].…”

Section: Introductionmentioning

confidence: 99%

Neuroblast Differentiation-Associated Protein Derived Polypeptides: AHNAK(5758-5775) Induced Inflammatory Reaction in Skin By Mast Cells Activation

Che

Song

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

Psoriasis is a chronic inflammatory skin disease. Mast cells significantly increase and activate in the lesions and are involved in psoriatic inflammation. Neuroblast differentiation-associated protein (AHNAK) mainly express in skin, esophagus and kidney, which participates in the differentiation of neurons, the formation of cytoskeletal structure muscular regeneration and the calcium homeostasis process. Whether AHNAK is involved in mast cell activation is unclear, and the mechanisms of AHNAK induced skin inflammation also needs investigation. To investigate whether Neuroblast differentiation-associated protein derived polypeptides: AHNAK(5758-5775) activates mast cells and induces skin inflammation contributing to psoriasis, wild-type mice were treated with AHNAK(5758-5775) to observe inflammatory cells infiltrated in skin and cytokines release in vivo. Release of inflammatory mediators by mouse primary mast cells, LAD2 cells and human neutrophils were measured in vitro. Neutrophils and mast cells were co-cultured to verify AHNAK(5758-5775)’ role in inflammation. Molecular docking analysis, molecular dynamics simulation and siRNA transfection were used to prove the receptor of AHNAK(5758-5775). AHNAK(5758-5775) caused skin inflammation in WT mice by recruitment of neutrophils and cytokines release. Moreover, AHNAK(5758-5775) does not directly activate neutrophils PPD, while it is via mast cells. ST2 seems to be a key receptor meditating the activation effect of AHNAK(5758-5775) on mast cells and lead to cytokines release. Altogether, we proposed the novel polypeptide: AHNAK(5758-5775), which might induce inflammation and participated in the occurrence and development of psoriasis by activating mast cells.

show abstract

Profiles of Innate Immune Cell Infiltration and Related Core Genes in Psoriasis

Cited by 3 publications

References 27 publications

Mannan‐binding lectin exacerbates the severity of psoriasis by promoting plasmacytoid dendritic cell differentiation via the signal transducer and activator of transcription 3–interferon regulatory factor 8 axis

Mannan‐binding lectin exacerbates the severity of psoriasis by promoting plasmacytoid dendritic cell differentiation via the signal transducer and activator of transcription 3–interferon regulatory factor 8 axis

Signaling pathways and targets of natural products in psoriasis treatment

Neuroblast Differentiation-Associated Protein Derived Polypeptides: AHNAK(5758-5775) Induced Inflammatory Reaction in Skin By Mast Cells Activation

Contact Info

Product

Resources

About