Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Faslpr mice

Julia Menke, Mei Yu Hsu, Katelyn T. Byrne, Julie A. Lucas, Whitney A. Rabacal, Byron P. Croker, Xiao Hua Zong, E. Richard Stanley, Vicki Rubin Kelley

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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-Faslpr mice. By constructing mutant MRL-Faslpr 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-Faslpr mice, but not in lupus-resistant BALB/c mice. UVB incites an increase in Møs, apoptosis in the skin, and CLE in MRL-Faslpr, but not in CSF-1-deficient MRL-Faslpr 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-Faslpr 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.

Original languageEnglish (US)
Pages (from-to)7367-7379
Number of pages13
JournalJournal of Immunology
Volume181
Issue number10
DOIs
StatePublished - Nov 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Menke, J., Hsu, M. Y., Byrne, K. T., Lucas, J. A., Rabacal, W. A., Croker, B. P., Zong, X. H., Stanley, E. R., & Kelley, V. R. (2008). Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Faslpr mice. Journal of Immunology, 181(10), 7367-7379. https://doi.org/10.4049/jimmunol.181.10.7367