Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Photosensitivity, defined as increased cutaneous erythema and inflammation after ultraviolet light (UV) exposure, is a hallmark of patients with systemic lupus erythematosus (SLE), cutaneous lupus erythematosus (CLE), and many other autoimmune conditions with skin involvement. Type I interferons (IFNs) are increased in SLE and CLE skin and contribute to a propensity for inflammatory responses by keratinocytes. We have identified IFNκ as a keratinocyte-expressed type I IFN whose expression is elevated in non-lesional SLE keratinocytes, which suggests that it may contribute to the propensity for inflammation in SLE skin. Apoptosis of keratinocytes is thought to be a central pathologic response that contributes to increased photosensitivity. However, the contribution of type I IFNs, including IFNκ, to apoptosis after UVB exposure is unknown. We thus examined the role of IFNκ in regulating UVB-induced keratinocyte apoptosis in order to determine whether type I IFNs contribute to photosensitivity predisposition.
Methods: Age and gender-matched control (n=5) and SLE (n=5) keratinocytes were isolated from non-lesional, non-sun exposed 6mm punch skin biopsies from the upper thigh and used at passages 3-5 for study. All patients gave written, informed consent and were treated according to the Declaration of Helsinki. IFNK -/- N/TERT keratinocytes were generated via CRISPR/Cas9. N/TERTs overexpressing IFNκ were generated via nucleofection of an IFNκ expressing plasmid followed by selection in G418. Primary keratinocytes and N/TERT keratinocyte lines were treated with or without 50mJ/cm2 UVB followed by TUNEL staining 8 hours after UVB treatment. In some cases, baricitinib was used to block IFN signaling prior to UVB treatment.
Results: As expected, we identified increased apoptosis in CLE lesional skin vs. normal skin, especially in the basal keratinocyte layer. Importantly, SLE non-lesional keratinocytes displayed increased apoptosis vs. healthy control keratinocytes after UVB treatment. This apoptotic process was dependent on IFNκ as deletion of this protein resulted in significantly diminished TUNEL staining after UVB exposure. Further, chronic overexpression of IFNκ in N/TERT keratinocytes also induced increased apoptosis after UVB. Finally, treatment of SLE and healthy control non-lesional keratinocytes with baricitinib to block IFN signaling significantly diminished UVB-mediated apoptosis.
Conclusion: IFNκ expression serves as a regulator of apoptotic responses to UVB in keratinocytes. In SLE non-lesional skin, chronic overexpression of IFNκ predisposes to increased apoptosis after UVB exposure, which leads to increased autoantigen exposure, cytokine/chemokine production, and inflammatory cell recruitment. This increased inflammatory response likely results in the enhanced UV-triggered erythema and skin eruptions in SLE patients. Downregulation of IFNκ may serve as an excellent, specific target to prevent photosensitivity in SLE patients.
To cite this abstract in AMA style:Hile G, Sarkar M, Liu J, Reed TJ, Gudjonsson J, Kahlenberg M. Interferon Kappa Regulates Apoptotic Response to UVB in Control and Lupus Keratinocytes [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/interferon-kappa-regulates-apoptotic-response-to-uvb-in-control-and-lupus-keratinocytes/. Accessed August 13, 2020.
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