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

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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
StatePublished - Nov 15 2008

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Cutaneous Lupus Erythematosus
Macrophage Colony-Stimulating Factor
Sunlight
Skin
Keratinocytes
Apoptosis
Macrophages
Inflammation

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Menke, J., Hsu, M. Y., Byrne, K. T., Lucas, J. A., Rabacal, W. A., Croker, B. P., ... 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.

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

In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 7367-7379.

Research output: Contribution to journalArticle

Menke, J, Hsu, MY, Byrne, KT, Lucas, JA, Rabacal, WA, Croker, BP, Zong, XH, Stanley, ER & Kelley, VR 2008, 'Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Faslpr mice', Journal of Immunology, vol. 181, no. 10, pp. 7367-7379.
Menke J, Hsu MY, Byrne KT, Lucas JA, Rabacal WA, Croker BP et al. Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Faslpr mice. Journal of Immunology. 2008 Nov 15;181(10):7367-7379.
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 Rubin. / Sunlight triggers cutaneous lupus through a CSF-1-dependent mechanism in MRL-Faslpr mice. In: Journal of Immunology. 2008 ; Vol. 181, No. 10. pp. 7367-7379.
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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 (M{\o})-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 M{\o}s, 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 M{\o}s that, in turn, release mediators, which induce apoptosis in keratinocytes. Thus, sunlight triggers a CSF-1-dependent, M{\o}-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.",
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