Spatial transcriptomics revealed that S1pr2 deletion in keratinocytes increases the MyD88/NF-kB pathway and psoriasis-related cytokine expression in the epidermis

The importance of the cross-talk between keratinocytes and immune cells in the pathogenesis of psoriasis has recently been reaffirmed. Recent studies have found that several S1PR functional antagonists, other than S1PR2, are effective in improving psoriasis. We performed spatial transcriptomics to map the immune cell landscape and its association with metabolic pathways in an imiquimod (IMQ)-induced psoriasis-like inflammation in S1pr2fl/fl K14-Cre mice that could not sense sphingosine-1-phosphate (S1P) in the epidermis through the S1PR2 receptor. Our analysis suggests that S1PR2 in keratinocytes plays a major role in psoriasis-like inflammation compared to other S1PRs. It acts as a down-regulator, inhibiting the recruitment of Th17 cells into the skin. Overall design: Mice at 8 weeks old of S1pr2fl/fl and S1pr2fl/fl K14-Cre were depilated on the back skin 1 day before the treatment, then received a daily topical dose of 62.5 mg of 5% IMQ cream for 7 days. Skin samples were collected, formalin-fixed, and paraffin-embedded. Skin samples from S1pr2fl/fl mouse treated with IMQ (S1pr2wtIMQ) and S1pr2fl/fl K14-Cre mouse treated with IMQ (S1pr2K14IMQ) were analyzed using spatial transcriptomics.