Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice
Graduate School of Biomedical Sciences; Laboratory of Molecular Autoimmune Disease
Medical Subject Headings
Adoptive Transfer; Animals; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression; Immunohistochemistry; Keratinocytes; Lupus Erythematosus, Systemic; Macrophage Colony-Stimulating Factor; Macrophages; Mice; Mice, Inbred MRL lpr; Mice, Transgenic; Skin Diseases; Sunlight
Life Sciences | Medicine and Health Sciences
Sunlight (UVB) triggers cutaneous lupus erythematosus (CLE) and systemic lupus through an unknown mechanism. We tested the hypothesis that UVB triggers CLE through a CSF-1-dependent, macrophage (Mo)-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 intradermally, we determined that CSF-1 induces CLE in lupus-susceptible MRL-Fas(lpr) mice, but not in lupus-resistant BALB/c mice. UVB incites an increase in Mos, 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 Mos that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, Mo-mediated destructive inflammation in the skin leading to CLE in lupus-susceptible MRL-Fas(lpr) but not lupus-resistant BALB/c mice. Taken together, CSF-1 is envisioned as the match and lupus susceptibility as the tinder leading to CLE.
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Citation: J Immunol. 2008 Nov 15;181(10):7367-79.
Journal of immunology (Baltimore, Md. : 1950)
Menke, Julia; Hsu, Mei-Yu; Byrne, Katelyn T.; Lucas, Julie A.; Rabacal, Whitney A.; Croker, Byron P.; Zong, Xiao-Hua; Stanley, E. Richard; and Kelley, Vicki R., "Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice" (2008). GSBS Student Publications. 1367.