2007 Environmental Triggers, Skin
While scientists have long known that sunlight’s ultraviolet rays can trigger cutaneous (skin) as well as systemic lupus in some people, it’s been unclear exactly how this happens.
Dr. Kelley was awarded Lupus Research Institute funding to explore her novel idea on exactly HOW sunlight exposure triggers skin and systemic lupus.
She started out with early evidence that ultraviolet light (UVB) stimulates the skin to produce a factor that recruits white blood cells. Using specially developed animal models, Dr. Kelley examined whether UVB-induced production of this factor in the skin leads to lupus.
Just a year after receiving her LRI grant, Dr. Kelley reported an important finding in November 2008’s Journal of Immunology, showing that the damaging sequence is triggered when sunlight stimulates the skin to produce something called Colony Stimulating Factor 1 (CSF-1).
She and colleagues showed that once CSF-1 is produced, it then recruits and modifies white blood cells, which in turn stimulates the most common form of skin lupus in genetically susceptible individuals: the red, scaly and inflamed lesions of discoid lupus that can permanently damage and scar the skin.
Dr. Kelley and colleagues are currently validating their findings in people with cutaneous lupus—the research was originally done in mice—and are also examining what role UVB-induced CSF-1 plays in triggering multi-organ “systemic” lupus (particularly lupus-related kidney disease).
She also is working to identify the genes a person inherits from their parents to make them susceptible to skin lupus in the first place—the “tinder”—as described in the journal article, which is then triggered by “the match” of CSF-1.
Exciting future studies are being planned, she said, to explore whether blocking CSF-1 with a topical (skin) lotion or other agent might provide greater therapeutic benefit than commercially available sunscreens that people with lupus currently use to protect themselves from sun exposure.
Notably, the Journal’s cover featured an image from Dr. Kelley’s research—a high-power photo of cutaneous lupus (discoid lupus) in the mouse.
Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice. Menke J, Hsu MY, Byrne KT, Lucas JA, Rabacal WA, Croker BP, Zong XH, Stanley ER, Kelley VR. J Immunol. 2008 Nov 15;181(10):7367-79.