HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Menke, J. Articles by Kelley, V. R. Search for Related Content PubMed PubMed Citation Articles by Menke, J. Articles by Kelley, V. R.

Sunlight Triggers Cutaneous Lupus through a CSF-1-Dependent Mechanism in MRL-Fas^lpr Mice ¹

Julia Menke^*, Mei-Yu Hsu, Katelyn T. Byrne^*, Julie A. Lucas^*, Whitney A. Rabacal^*, Byron P. Croker, Xiao-Hua Zong, E. Richard Stanley and Vicki R. Kelley^2,*

^* Laboratory of Molecular Autoimmune Disease, Renal Division, Department of Medicine, and Department of Pathology, Program in Dermatopathology, Brigham and Women’s Hospital, Boston, MA 02115; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32608; and Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Lupus Research Institute (to V.R.K.), Deutsche Forschungsgemeinschaft Grant ME-3194/1-1 (to J.M.), and Ruth L. Kirschstein National Research Service Award F32 DK078416-01 (to J.L.).

² Address correspondence and reprint requests to Dr. Vicki Rubin Kelley, Harvard Institutes of Medicine, 4 Black Fan Circle, Boston, MA 02115. E-mail address: vkelley{at}rics.bwh.harvard.edu

³ Abbreviations used in this paper: CLE, cutaneous lupus erythematosus; MRL-++, MRL/MpJ-+/+; MRL-Fas^lpr, MRL/MpJ-Fas^lpr/Fas^lpr; Mø, macrophage; BM, bone marrow; BMMø, BM-derived Mø; DC, dendritic cell; TEC, tubular epithelial cell; EGFP, enhanced GFP; PI, propidium iodide.