519 <i>Staphylococcus</i> colonization drives IFN-mediated monocyte recruitment and skin barrier disruption in cutaneous lupus erythematosus lesions

Objectives/Goals: Cutaneous lupus erythematosus (CLE) is an inflammatory skin manifestation of lupus. CLE lesions are frequently colonized by Staphylococcus aureus , a microbe known to promote IFN production and inflammation. Here, we investigate whether type I IFN and inflammatory gene signatures in CLE lesions can be modulated with a topical antibiotic treatment. Methods/Study Population: SLE patients with active CLE lesions (n = 12) were recruited and randomized into a week of topical treatment with either 2% mupirocin or petroleum jelly vehicle. Paired samples were collected before and after 7 days of treatment to assess microbial lesional skin responses. Microbial samples from nares and lesional skin were used to determine baseline and posttreatment Staphylococcus abundance and microbial community profiles by 16S rRNA gene sequencing. Inflammatory responses were evaluated by bulk RNA sequencing of lesional skin biopsies. Immunophenotyping of CLE lesions was performed using CIBERSORTx to deconvolute the RNA-seq data into predicted cell populations impacted by treatment. Results/Anticipated Results: We identified 173 differentially expressed genes in CLE lesions after topical mupirocin treatment. Mupirocin treatment decreased the abundance of Staphylococcus associated with CLE lesions without altering the overall diversity of the skin microbiota relative to vehicle. Decreased lesional Staphylococcus burden correlated with decreased IFN pathway signaling and inflammatory gene expression and increased barrier dysfunction. Interestingly, mupirocin treatment lowered skin monocyte levels, and this mupirocin-associated depletion of monocytes correlated with decreased inflammatory gene expression. Discussion/Significance of Impact: Mupirocin treatment decreased lesional Staphylococcus burden and this correlated with decreased IFN signaling and inflammatory gene expression. This study suggests a topical antibiotic could be employed to decrease lupus skin inflammation and type I IFN responses by reducing Staphylococcus colonization.