Rachel Holle
Research Mentor(s): Joanne Kahlenberg
Mentor Department: Internal Medicine, Division of Rheumatology
Authors: Rachel Holle, Rezvan Moallemian, Lin Zhang, J. Michelle Kahlenberg
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 26
Abstract
In systemic lupus erythematosus (SLE), exposure to ultraviolet (UV) light is a known trigger of cutaneous inflammation. However, the impact of UVB radiation on melanocytes in SLE, particularly in the context of type I interferon (IFN-a) signaling, remains incompletely understood. Here, we investigate these effects using primary human melanocytes and cell lines, which were cultured and exposed to IFN-alpha followed by UVB irradiation. Subsequent analyses included RT-PCR and RNA sequencing to examine inflammatory responses and interferon signaling. We find that pro-inflammatory cytokines IL-6, TNF-alpha, and CCL5 were significantly upregulated following IFN-alpha priming and was further enhanced by UVB in a dose dependent manner. In addition, interferon-stimulated genes IFNB, MX1, IFIT30, and ISG15 showed a robust induction, especially in the IFN-alpha-primed and UVB-treated groups, while in contrast MITF and TYRP-1 expression remained unchanged. STING was induced by UVB but showed reduced expression with higher UVB exposure. Also, stimulation of primary melanocytes with IFN-a followed by RNA-seq analysis revealed a significant upregulation of interferon-related pathways, including interferon alpha/beta signaling, interferon gamma signaling, and antigen presentation pathways. Taken together, these findings suggest that IFN- alpha primes melanocytes for an enhanced inflammatory and interferon responses upon UVB exposure without significantly affecting melanogenesis genes.
