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A Low-Modulus Phosphatidylserine-Exposing Microvesicle Alleviates Skin Inflammation via Persistent Blockade of M1
Zihao Zhang1, Yidi Mo1, Shengxia Xu1
1Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology, Jinan University, Guangzhou 510632, China.
Abstract:
Inflammatory skin diseases comprise a group of skin conditions characterized by damage to skin function due to overactive immune responses. These disorders not only impair the barrier function of the skin but also deteriorate the quality of life and increase the risk of psychiatric issues. Here, a low-modulus phosphatidylserine-exposing microvesicle (deformed PSV, D-PSV) was produced, characterized, and evaluated for its potential therapeutic function against skin diseases. Compared to conventional PSVs (C-PSVs), D-PSVs exhibited a more robust and longer-lasting inhibitory effect on the inflammatory response triggered by lipopolysaccharides and interferon-γ in a primary bone marrow-derived macrophage model. Transcriptome analysis indicated that the inhibitory effect of D-PSVs was mainly achieved by modulating inflammation-related signaling pathways, leading to a reduction in the expressions of pro-inflammatory genes. In an imiquimod-induced psoriatic dermatitis mouse model, topical application of D-PSVs effectively mitigated inflammation in the skin microenvironment and reduced lesion severity. These improvements were attributed to the superior skin permeability and more persistent adhesion of D-PSVs to macrophages compared with C-PSVs. In summary, this macrophage-targeted microvesicle offers a promising non-invasive approach to managing inflammatory skin diseases by persistently inhibiting M1 macrophage polarization and restoring immune microenvironment balance.
Insights
Researchers developed deformed phosphatidylserine-exposing microvesicles (D-PSVs) that effectively treat inflammatory skin diseases. These D-PSVs target macrophages, reduce inflammation, and improve skin conditions by modulating immune responses.
Area of Science:
- Immunology
- Dermatology
- Biotechnology
Background:
- Inflammatory skin diseases impair skin barrier function, quality of life, and mental health.
- Overactive immune responses are central to these conditions.
- Current treatments may have limitations in efficacy and delivery.
Purpose of the Study:
- To develop and evaluate a novel microvesicle-based therapy for inflammatory skin diseases.
- To investigate the therapeutic potential of low-modulus phosphatidylserine-exposing microvesicles (D-PSVs).
- To assess the efficacy of D-PSVs in modulating macrophage polarization and skin inflammation.
Main Methods:
- Production and characterization of deformed phosphatidylserine-exposing microvesicles (D-PSVs).
- In vitro assessment of D-PSV anti-inflammatory effects on macrophages stimulated with lipopolysaccharides and interferon-γ.
- Transcriptome analysis to identify D-PSV-modulated signaling pathways.
- In vivo evaluation of D-PSV efficacy in an imiquimod-induced psoriatic dermatitis mouse model.
Main Results:
- D-PSVs demonstrated a more robust and sustained inhibition of inflammatory responses compared to conventional PSVs (C-PSVs).
- Transcriptome analysis revealed that D-PSVs modulate inflammation-related pathways, reducing pro-inflammatory gene expression.
- Topical D-PSV application significantly reduced skin inflammation and lesion severity in a mouse model.
- Enhanced skin permeability and macrophage adhesion of D-PSVs contributed to their therapeutic effects.
Conclusions:
- Macrophage-targeted D-PSVs offer a promising non-invasive therapeutic strategy for inflammatory skin diseases.
- D-PSVs effectively inhibit M1 macrophage polarization and restore immune microenvironment balance.
- The unique properties of D-PSVs lead to superior therapeutic outcomes in managing skin inflammation.
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