RGD Reference Report - Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice. - Rat Genome Database
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Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Fas(lpr) mice.

Authors: Menke, J  Hsu, MY  Byrne, KT  Lucas, JA  Rabacal, WA  Croker, BP  Zong, XH  Stanley, ER  Kelley, VR 
Citation: Menke J, etal., J Immunol. 2008 Nov 15;181(10):7367-79.
RGD ID: 7257572
Pubmed: (View Article at PubMed) PMID:18981160

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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Csf1  (colony stimulating factor 1)

Genes (Mus musculus)
Csf1  (colony stimulating factor 1 (macrophage))

Genes (Homo sapiens)
CSF1  (colony stimulating factor 1)


Additional Information