# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 4 Sporiasis and Associated Dermatologic Disorders
PG, especially PGD2, potentially plays a role in the recruitment of type 2 immune cells in the skin lesions of AD. Activated MCs are the primary source of PDG2 production. The receptor CRTH2, crucial for PGD2, is expressed on various type 2 immune cells like Th2 cells, eosinophils, and basophils. CRTH2 stimulates chemotaxis and degranulation in Th2 cells, eosinophils, and basophils. Recent findings suggest that human ILC2 cells also express CRTH2, and the PGD2-CRTH2 signaling pathway facilitates cytokine production and chemotaxis in ILC2 cells. In AD patients, an increase in circulating CRTH2+ cells has been observed [62]. LTs may also contribute to Th2 cell infiltration in AD lesions through LTB4-BLT1 signaling. BLT1, the receptor for LTB4, is expressed in various cells, including neutrophils and Th2 cells. Scratching leads to neutrophil infiltration in the skin, where LTB4 produced by these neutrophils acts on BLT1 receptors expressed on neutrophils and Th2 cells, aiding their infiltration into the skin. Studies have shown the therapeutic potential of 5-lipoxygenase inhibitors in managing AD, indicating the involvement of LTB4 in AD progression. Additionally, cysteinyl leukotrienes (CysLTs), particularly CysLTE4, produced abundantly by skin mast cells, promote Th2 cytokine production via the CysLTI receptor. These CysLTs also induce migration, cytokine production, and receptor expression in ILC2 cells. The effects of CysLTE4 on Th2 and ILC2 cells are synergistically boosted by PGD2. Therefore, targeting PGD2 and CysLTE4 or their receptors collectively may present a novel therapeutic avenue for addressing AD. Interestingly, PGE2 and PGD2 have been found to hasten the recovery of skin barrier function following mechanical scratching, suggesting a dual role for PGE2 mediated through different receptors in skin barrier maintenance. PGE2 facilitates pruritus in AD by inducing the release of histamine from mast cells. Numerous prostanoids and LTs have been found in abundance in human psoriatic skin lesions. While their specific roles in psoriasis are not entirely understood, the use of advanced mouse psoriasis models, like the imiquimod-induced psoriasis model, has shed light on the involvement of these lipid mediators in psoriatic dermatitis. In this model, mice lacking TP receptors and wild-type mice treated with a TXA2 synthase inhibitor showed reduced dermatitis, along with decreased IL-17 production from \(\gamma\)6 T cells in the skin. This suggests that TXA2-TP signaling may exacerbate psoriatic dermatitis by promoting IL-17 production in psoriatic skin lesions. Additionally, PGE2, another prostanoid, is implicated in promoting psoriatic dermatitis through the regulation of IL-23/IL-17 pathways [62]. IL-23 plays a crucial role in psoriasis development by stimulating the formation and activation of Th17 cells. Fibroblast-produced PGE2 has been shown to enhance IL-23 production from dendritic cells in vitro, supporting Th17 cell expansion. Moreover, PGE2 from Th17 cells boosts the expression of an IL-23 receptor subunit gene through EP2 and EP4, promoting Th17 cell generation. In a mouse psoriasis model induced by IL-23, deleting both EP2 and EP4 on T cells inhibited Th17 cell accumulation in the skin and halted psoriatic lesions development. Therefore, targeting PGE2-EP2/EP4 signaling may hold promise as a therapeutic strategy for reducing Th17 cells in psoriasis. The potential roles of LTs in psoriasis have also been explored. In the imiquimod-induced psoriasis model, LTB4-BLT1 signaling in neutrophils expedited their skin infiltration by cooperating with CXCR2 and intensified psoriasis development. Additionally, LTB4 influenced skin DCs and \(\gamma\)8 T cells through BLT1, enhancing their migration and cytokine production, and contributing to psoriatic dermatitis progression. The LTB4-BLT1 pathway may play a part in the pathogenesis of psoriasis through these mechanisms [62]. It has been proven that both psoriasis and AD are closely related to obesity.