# Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis
## 1 Introduction  
Psoriasis is a chronic and recurrent inflammatory skin disease, which affects 2-4% of the population worldwide [1]. Based on the clinical manifestations, psoriasis can be classified into four main subtypes, including plaque psoriasis (psoriasis vulgaris), guttate psoriasis, pustular psoriasis and erythroderric psoriasis. Among them, plaque psoriasis is the most prevalent form, accounting for 80-90% of all cases. Psoriasis is clinically prone to developing erythema, scales and plaque on the scalp, trunk and buttocks [2]. The pathogenesis of psoriasis is a complex process involving interactions between the immune system, environment and genetic predisposition factors; therefore, it still has not been fully elucidated. Currently, the IL-23/IL-17 axis has been considered as the key mechanism underlying the pathogenesis of psoriasis. Activated dendritic cells (DCs) in the dermis can induce the differentiation of Th17 cells through the release of IL-23 and IL-6. Th17 cells, then,induce aberrant proliferation and differentiation of keratinocytes by producing IL-17A/F and IL-22. The abnormal keratinocytes in turn activate DCs by producing proinflammatorycytokines, such as TNF-\(\alpha\), IL-18, IL-6 and LL-37-self-DNA/RNA complexes [2,3]. Based on the therapeutic targets of the IL-23/IL-17 axis, many biologics have been developed to treat psoriasis. Although these biologics can effectively alleviate psoriasis, skin lesions often recur upon biologics withdrawal [4,5]. Thus, more studies are needed to further understand how immune cells interact with each other or with non-immune cells during the onset and relapse of psoriasis. Intercellular communication is crucial for the development and maintenance of these diseases. Recently, exosomes have been recognized as important mediators of intercellular communications [6]. Exosomes are small lipid bilayer vesicles secreted by cells, with a diameter range from 30 to 150 nm [7]. They express CD81, CD63 and CD9, and carry many biologically active cargos, such as nucleic acids (DNA, mRNA, miRNA, etc. ), specific proteins, lipids and metabolites. These cargos in exosomes are involved in different intercellular communications and regulate cellular biological processes, including metabolism, cell proliferation/differentiation, immune response and signal transduction [8]. Therefore, exosomes, as transport vehicles, not only retain the function of parental cells but also regulate the function of neighboring cells. Studies have shown that exosomes participate in important skin immunopathology, including psoriatic skin inflammation. The exosomes from both immune and non-immune cells in psoriaticic lesions play an important role in the pathogenesis of psoriasis [9]. The biologically active cargo in these exosomes can accelerate the development of psoriasis by regulating expression of genes and signaling pathways of neighboring cells [10, 11, 12]. Hence, further exploration of the mechanisms underlying intercellular communications in psoriaticic lesions helps us to understand the pathogenesis of psoriasis. Moreover, exosomes can serve as biomarkers for monitoring the effectiveness of psoriasis treatment because the cargoes or chemical compositions of exosomes change with the progression of psoriasis. More importantly, exosomes can be used as ideal delivery platforms for psoriasis treatment. Previous studies have revealed that exosomes derived from mesenchymal stem cells (MSCs) exert anti-inflammatory effects on psoriasis [13]. Additionally, engineered exosomes can act as delivery systems for efficient delivery of proteins, nucleic acids and/or drugs due to their low immunogenicity, good stability and ability to fuse with target cells. In this review, we have summarized the biogenesis of exosomes, immunoregulatory function of exosomes derived from immune or non-immune cells and their potential roles in psoriasis as biomarkers, delivery systems or therapeutic agents.