Sphingosine 1-phosphate receptor 2 in keratinocytes plays a key role in reducing inflammation in psoriasis

• DOI: 10.3389/fimmu.2024.1469829
• Publication Date: 2024-09-26T04:32:26Z
• Authors: Kana Masuda-Kuroki; Shahrzad Alimoham...; Samantha Lowry; Anna Di Nardo
• Keywords: Proinflammatory cytokine; Interleukin 22; TLR7

Background Psoriasis is an inflammatory skin condition where immune cells play a significant role. The importance of the cross-talk between keratinocytes and in pathogenesis psoriasis has recently been reaffirmed. Recent studies have found that several S1PR functional antagonists, other than S1PR2, are effective improving psoriasis. This study aims to investigate role S1PR2 psoriasis, not investigated before. Methods Spatial transcriptomics, RT-qPCR, flow cytometry were used map cell landscape its association with metabolic pathways imiquimod (IMQ)-induced psoriasis-like inflammation S1pr2 fl/fl K14-Cre mice could sense sphingosine-1-phosphate (S1P) epidermis through receptor. Results Our analysis suggests plays major compared S1PRs. It acts as down-regulator, inhibiting recruitment Th17 into skin. In IMQ-induced skin, both -/- showed higher expressions proinflammatory cytokines such TNF-α, IL-17A, IL-1β together MyD88/NF-κB pathway wild-type mice. Remarkably, IMQ-treated mice, deletion only resulted larger population skin-draining lymph nodes. Other modulators did improve worsening caused by deficiency keratinocytes. Conclusion reaches two main conclusions: signals from central creating environment promotes development stimulating instead suppressing it, represents potential therapeutic approach for