Sunlight Triggers Cutaneous Lupus through a Colony Stimulating Factor-1 (CSF-1) Dependent Mechanism in MRL-Faslpr mice

• Published in: The Journal of immunology (1950) 2008-11, Vol.181 (10), p.7367-7379
• Main Authors: Menke, Julia, Hsu, Mei-Yu, Byrne, Katelyn T., Lucas, Julie A., Rabacal, Whitney A., Croker, Byron P., Zong, Xiao-Hua, Stanley, E. Richard, Kelley, Vicki R.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

Sunlight (UVB) triggers cutaneous (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mø) -mediated mechanism in MRL- Fas lpr mice. By constructing mutant MRL- Fas lpr strains expressing varying levels of CSF-1 (high, intermediate, none), and use of an ex-vivo gene transfer to deliver CSF-1 intra-dermally, we determined that CSF-1 induces CLE in lupus-susceptible, MRL- Fas lpr mice, but not in lupus-resistant, BALB/c mice. Notably, UVB incites an increase in Mø, apoptosis in the skin and CLE in MRL- Fas lpr , but not in CSF-1-deficient MRL- Fas lpr mice. Furthermore, UVB did not induce CLE in BALB/c mice. Probing further, UVB stimulates CSF-1 expression by keratinocytes leading to recruitment and activation of Mø that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mø-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL- Fas lpr , but not lupus-resistant BALB/c mice. Taken together, we envision CSF-1 as the “match” and lupus-susceptibility as the “tinder” leading to CLE.