Peroxisome Proliferator-Activated Receptor-α Activation Inhibits Langerhans Cell Function

Sandrine Dubrac , Patrizia Stoitzner , Daniela Pirkebner , Andreas Elentner , Kristina Schoonjans (1) , Johan Auwerx (1) , Sem Saeland , Paul Hengster , Peter Fritsch , Nikolaus Romani , Matthias Schmuth

1 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

Abstract 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-α (PPARα) activation modulates LC function. Our results show that PPARα is expressed in immature LC and is down-regulated in mature LC suggesting that an early decrease of PPARα expression in LC may allow them to mature after contact with an Ag. We further show that pharmacologic PPARα activation inhibits LC maturation, migratory capacity, cytokine expression, and the ability to drive T cell proliferation. Moreover, PPARα activation inhibits NF-κB but not stress-activated protein kinase/JNK, p38MAPK, and ERK1/2. In conclusion, PPARα 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.

Domaines: Immunologie

Sandrine Dubrac, Patrizia Stoitzner, Daniela Pirkebner, Andreas Elentner, Kristina Schoonjans, et al.. Peroxisome Proliferator-Activated Receptor-α Activation Inhibits Langerhans Cell Function. Journal of Immunology, 2007, 178 (7), pp.4362-4372. ⟨10.4049/jimmunol.178.7.4362⟩. ⟨hal-04111681⟩