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Activation Inhibits Langerhans Cell Function1
* Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria;
Kompetenzzentrum Medizin Tirol-Zentraler Informatik Dienst Laboratory, Department of General and Transplant Surgery, Innsbruck Medical University, Innsbruck, Austria;
Institut de Génétique et Biologie Cellulaire et Moléculaire, Illkirch, France; and
DermImmune, Lyon, France
Epidermal Langerhans cells (LC) play a pivotal role in initiating and maintaining primary immune responses in the skin. In the present study, we asked whether peroxisome proliferator-activated receptor-
(PPAR) activation modulates LC function. Our results show that PPAR is expressed in immature LC and is down-regulated in mature LC suggesting that an early decrease of PPAR expression in LC may allow them to mature after contact with an Ag. We further show that pharmacologic PPAR activation inhibits LC maturation, migratory capacity, cytokine expression, and the ability to drive T cell proliferation. Moreover, PPAR activation inhibits NF-
B but not stress-activated protein kinase/JNK, p38MAPK, and ERK1/2. In conclusion, PPAR activation by endogenous ligands may provide a molecular signal that allows LC to remain in an immature state within the epidermis for extended periods of time despite minor environmental stimuli.
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 the Austrian Science Fund Grants P-16990 (to M.S.) and, in part, L120-B13 (to N.R.) and the Research Fund of the University of Innsbruck (Grant M55 (to M.S.)).
2 Address correspondence and reprint requests to Dr. Sandrine Dubrac, Department of Dermatology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. E-mail address: sandrine.dubrac{at}i-med.ac.at
3 Abbreviations used in this paper: PPAR, peroxisome proliferator-activated receptor; DC, dendritic cell; LC, Langerhans cell; EC, epidermal cell; SAPK, stress-activated protein kinase; 7-AAD, 7-aminoactinomycin D; MHC II, MHC class II; DAPI, 4',6'-diamidino-2-phenylindole; TNCB, 2,4,6-trinitro-1-chlorobenzene; 4PB, 4 phenylbutyric acid.
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