# Roles for Exosomes in the Pathogenesis, Drug Delivery and Therapy of Psoriasis
## 3 The Immunological Function of Exosomes That Are or Are Not Associated with Soriasis
### Immune Cell-Derived Exosomes  
#### 3.1.1 Dendritic Cell-Derived Exosomes  
Dendritic cells (DCs) are innate immune cells that bridge innate and adaptive immunity by acting as professional APCs and inducing T cell-mediated adaptive immunity. Pathogenic roles for both plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) have been highlighted in psoriasis [2]. In the initial phases of psoriasis development, pDCs are stimulated by self-DNA-LL37 complexes, which are released by keratinocytes (KCs), and then produce IFN-\(\alpha\), which subsequently promotes the maturation and activation of bystander mDCs. Upon activation, mDCs secrete IL-12 and IL-23, which in turn induce naive T cell differentiation into Th1 and Th17 cells [3]. It has been reported that DC-derived exosomes positively impact the immune system, depending on the maturity of the immune cells [9]. Exosomes released from mature DCs carried MHC-I/II and costtimulatory molecules, which were critical for activating T cell \begin{table}
\begin{tabular}{p{113.8 pt} p{113.8 pt} p{113.8 pt} p{113.8 pt}} \hline \hline
**Source Cells** & **Contents** & **Target Cells** & **Effects** & **Ref.** \\ \hline \multirow{8}{*}{T cells} & \multirow{8}{*}{PLA2} & \multirow{8}{*}{CD1a-expressing cells} & \multirow{8}{*}{Increasing the generation of neolipid antigens in CD1a-expressing cells, which were subsequently recognized by lipid-specific CD1a-reactive T cells from psoriatic patients, thus inducing the production of IL-17A and IL-22} & \multirow{8}{*}{[36]} \\  & & & & Stimulating mast cells to degranulate and release IL-24, which in turn activated keratinocytes & \\  & & & Converting extracellular & \\  & & & adenosine-S-monophosphate to adenosine, thus promoting interactions with adenosine receptors expressed on target cells & \\  & & & & Inhibiting proliferation and IFN-\(\gamma\) secretion of Th1 cells & \\ \multirow{2}{*}{Non-immune cells} & \multirow{2}{*}{Let-7d} & \multirow{2}{*}{Th1 cells} & \multirow{2}{*}{Upregulating mRNA expression of endogenous \(\beta\)-Defensin 2, CCL20, CXCL1, CXCL3, CXCL5, CXCL6} & \multirow{2}{*}{[40]} \\  & & & & \(\beta\)-Defensin 2 in HaCaT cells & \\  & & & & Inducing the release of proinflammatory & \\  & & & & cytokines (IL-16, IL-6, IL-8 and TNF-\(\alpha\)) and chemokines (CXCL1) in HaCaT cells through Ahh signaling & \\  & & & & cells through Ahh signaling & \\  & & & & Enhancing the proliferation of CD* and CD* & \\  & & & & T cells in vitro & \\  & & & & promoting T cell differentiation into Th1/Th17 cells & \\  & & & & cells under psoriatic conditions & \\  & & & & Inducing maturation of DCs and their & \\  & & & & production of IL-6, IL-10 and IL-12 & \\  & & & & Increasing the release of NETs and production of IL-6, IL-8 and TNF-\(\alpha\) in neutrophils by activating NF-\(\kappa\)B and p38 MAPK pathways, thus exacerbating psoriatic skin lesions in mice & \\  & & & & Promoting macrophage polarization through & \\  & & & & & \\  & & & & T cells in vitro & \\  & & & & promoting T cell differentiation into Th1/Th17 cells & \\  & & & & cells under psoriatic conditions & \\  & & & & Inducing maturation of DCs and their & \\  & & & & production of IL-6, IL-10 and IL-12 & \\  & & & & Increasing the release of NETs and production of IL-6, IL-8 and TNF-\(\alpha\) in neutrophils by activating NF-\(\kappa\)B and p38 MAPK pathways, thus exacerbating psoriatic skin lesions in mice & \\  & & & & Promoting macrophage polarization through & \\  & & & & \\  & & & & T cells in vitro & \\  & & & & inhibiting epidermal hyperplasia and & \\  & & & & increasing the levels of filaggrin and HAS1 by augmenting the expression of PPAR\(\alpha\) in HaCaT cells & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: _Cont._mediated adaptive immunity [31]. Exosomes derived from mature or even immature DCs also promoted the activation of CD4\({}^{+}\) T cells and the secretion of Th1-cytokines, such as IFN-\(\gamma\)[32]. In addition, DC-derived exosomes could be captured by CD8\({}^{+}\) DCs with high levels of LFA-1.