Extracellular Vesicles and Their Role in Skin Inflammatory Diseases: From Pathogenesis to Therapy

Abstract

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are released into the extracellular space by almost all known cell types. They facilitate communication between cells by transferring bioactive molecules, which impact both physiological processes and the development of diseases. EVs play a crucial role in the pathogenesis of various diseases by participating in multiple pathological processes. They contribute to disease progression by triggering cytokine release, modulating immune cell activity, and inducing inflammatory and immune responses. Beyond their pathological implications, EVs also offer significant therapeutic potential. Both natural and engineered EVs show great potential in the fields of targeted therapy, drug delivery, and immune modulation in dermatological applications. The development of EV-based treatments is showing promise in advancing patient outcomes, particularly in chronic inflammatory and immune-mediated skin conditions. This review comprehensively examined the biogenesis, classification, and functional roles of EVs, including advanced methods for their isolation and characterization. Furthermore, we summarized recent studies highlighting the involvement of EVs in four major inflammatory skin diseases: psoriasis, atopic dermatitis, systemic lupus erythematosus, and wound healing.

Keywords: atopic dermatitis; extracellular vesicles; psoriasis; systemic lupus erythematosus; wound healing.

Figure 1

Keratinocyte-derived EVs modulate immune cells and promote inflammation in psoriasis. EVs released from keratinocytes treated with recombinant IL-17A (rIL-17A) and IL-23 (rIL-23) exhibit elevated levels of antimicrobial peptide (AMP) mRNAs, such as human β-defensin 2 (hBD2) and S100A12 [83]. Long-term IL-17A exposure further enhances β-defensin 2 expression and increases mRNA levels of neutrophil chemoattractants within EVs [82]. EVs from psoriasis-related, cytokine-treated keratinocytes can induce neutrophil extracellular trap formation (NETosis) in neutrophils [83]. Keratinocyte-derived EVs enriched with leucine-rich α-2-glycoprotein 1 (LRG1) promote M1 macrophage polarization via the TGFβR1 signaling pathway, leading to upregulation of pro-inflammatory genes [81]. EVs from inflamed keratinocytes transfer miR-381-3p to CD4⁺ T cells, promoting Th1 and Th17 polarization and thereby contributing to psoriasis progression [74]. ↑: Upregulation, activation, or increased expression, activity, or level.