Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.
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 (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 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 Møs, 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 Møs 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, CSF-1 is envisioned as the match and lupus susceptibility as the tinder leading to CLE.
Menke
Julia
J
Laboratory of Molecular Autoimmune Disease, Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Hsu
Mei-Yu
MY
Byrne
Katelyn T
KT
Lucas
Julie A
JA
Rabacal
Whitney A
WA
Croker
Byron P
BP
Zong
Xiao-Hua
XH
Stanley
E Richard
ER
Kelley
Vicki R
VR
D019264:Adoptive Transfer; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000276:immunology / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D012871:Skin Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D013472:Sunlight / Q000009:adverse effects*
D016173:Macrophage Colony-Stimulating Factor