703 S. epidermidis increases contact sensitization inflammation through the S1P receptor 2

Background: Sphingosine-1-phosphate (S1P) has been identified as a prominent signaling molecule that regulates the fundamental functions of keratinocytes and other skin immune cells. S1P can be generated inside by sphingosine kinases, but it also in intercellular space due to endogenous commensal bacterial ceramidase activity. interaction with its receptor S1PR2 epidermis maintains permeability barrier; however, little is known about role contact sensitization (ACD) or bacteria during ACD. Hypothesis aims: Our analysis genome-wide association study conducted on gene repositories at NIH showed increased after ACD subjects. These findings, together previous knowledge controls permeability, led us hypothesize S1P-S1PR2 involved inflammation Results: After dibutyl squarate (SADBE) application induce ACD, Filaggrin 2 were significantly lowered both wild-type (WT) S1PR2fl/flK14Cre mice. Applying bacteria, S.epidermidis (SE) further decreased ACD-WT ACD-S1PR2fl/flK14Cre. qPCR mRNAs Claudin1 Occludin upregulated not The ear thickness SE-treated ACD-S1PR2fl/flK14Cre was lower than ACD-WT. Consistent this result, SE enhanced cytokine mRNA expression, such IL1β, CXCL1, CXCL2, only ACT-S1PR2fl/flK14Cre. Conclusion: results confirm essential for tight junction recovery, block recovery through pathways. suggest worsens when present reduces absent, supporting hypothesis increases receptor.