# Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis
## 5 Exosome-Based Therapeutic Applications in Soriasis  
### Exosomes as Therapeutic Agents for Soriasis Treatment  
Recently, exosomes have received wide attention in terms of their potential application in the treatment of autoimmune diseases, including psoriasis [87], due to their immunomodulatory functions and effects (Figure 2). Previous studies have proven that exosomes from stem cells, such as umbilical cord MSCs (UCMSCs), embryonic stem cell-derived MSCs (ESC-MSCs) and adipose tissue-derived stem cells (ASCs), can alleviate psoriasis-like inflammation. [PERSON] and [PERSON] et al. investigated whether ESC-MSC-derived exosomes could alleviate psoriasisiform skin inflammation using a mouse model of IMQ-induced psoriasis. They  
Figure 2: The mechanisms underlying therapeutic effects of exosomes on psoriasis. Embryonic stem cell-derived mesenchymal stem cell (ESC-MSC)-exosomes inhibit C5b-9 complex formation in psoriatic skin, resulting in a reduction in neutrophil extracellular traps (NETs) formation and IL-17 release by neutrophils. Umbilical cord mesenchymal stem cell (UCMSC)-exosomes ameliorate psoriasisform skin inflammation in mice by suppressing the IL-23/IL-17 axis by inhibiting the activation of DCs and CCL20 release from KCs. Umbilical cord blood mononuclear cell (UCB-MNC)-exosomes alleviate acanthosis by restoring the balance of Th17/Treg in IMQ-induced psoriatic mice. Serum-derived exosomes containing miR-6785-5p alleviate psoriasis-like skin lesions by inhibiting the abnormal proliferation and inflammatory state of keratinocytes by interfering with the MNK2/p-eIF4E axis. Adipose tissue-derived stem cell (ASC)-exosomes suppress the production of IL-18, IL-6 and TNF-\(\alpha\) and the expression of Nov2 and Nov4, and they induce autophagy in HaCaT cells. (Upward, vertical and red arrows denote increasing, while downward, vertical and red arrows indicate decreasing). found that ESC-MSC-exosomes were mainly localized in the stratum corneum of the skin because they were prevented from penetrating into the epidermis by the layers of tight junctions found in the stratum granulosum. A topically applied emulsion of ESC-MSC-exosomes significantly inhibited C5b-9 complex formation by CD59, resulting in a reduction in IL-17 released by NETs of neutrophils [13; 88]. Additionally, another study examined the therapeutic effects of UCMSC-derived exosomes on psoriasis using a mouse model of IMQ-induced psoriasis. It was found that UCMSC-exosomes expressed CD9, CD63 and CD81. Subcutaneous injection of these UCMSC-exosomes could significantly ameliorate PASI scores and psoriatic symptoms, such as skin thickness, scaling and erythema. Furthermore, UCMSC-exosomes significantly decreased the expression of p-STAT3, IL-17, IL-23 and CCL20 in both psoriatic mice and HaCaT cells. The in vitro experiments also showed that UCMSC-exosomes inhibited IL-23 secretion from DCs. These results suggest that UCMSC-exosomes may ameliorate psoriasisform skin inflammation in mice by suppressing the IL-23/IL-17 axis by inhibiting the maturation and activation of DCs [89]. Additionally, although ASC-derived exosomes were reportedly involved in the pathogenesis of psoriasis, the ASC-exosomes could also decelerate the development of psoriasis. An in vitro study recently found that ASC-exosomes suppressed the production of proinflammatory cytokines (IL-1\(\beta\), IL-6 and TNF-\(\alpha\)) and expression of oxidative stress-related factors (Nox2 and Nox4) and induced autophagy in HaCaT cells. These effects were attributed to the restoration of autophagy of HaCaT cells by ASC-exosomes [90]. In addition to stem cells, exosomes derived from other types of cells have also been reported to exert anti- psoriaticatic effects. [PERSON] et al. explored the therapeutic potential of umbilical cord blood mononuclear cells (UCB-MNCs)-derived exosomes for psoriasis. They found that UCB-MNC-exosomes could predispose macrophages to become an anti-inflammatory phenotype.