Aryl hydrocarbon receptor (AhR) is an environmental sensor for immune responses. In skin, AhR is expressed in several cells, including keratinocytes and Langerhans cells (LC). The current evidence of how AhR would activate or inhibit skin immune responses is controversial, likely due to the differential role of AhR in different cells and different haptens or peptides used. We then crossbred Langerin-Cre or CD11c-Cre with AhR-loxP (AhRFL/FL) to generate Langerin-AhR+/- or -/- (LC) and CD11c-AhR-/- (dendritic cells) to address the role of AhR in langerin- or CD11c-expressing cells using epicutaneous ovalbumin sensitization. The result showed that Langerin-AhR-/- mice but not CD11c-AhR-/- mice showed decreased numbers of epidermal LC in epicutaneous ova sensitization. Langerin-AhR-/- mice also showed an enhancement of Th2 (increased IL-4 and IL-5) and Treg (increased IL-10) responses in vitro when their lymph node cells were challenged with Ova, although the numbers of Treg in lymph nodes remained similar. Ova-specific IgE blood level was increased in Langerin-AhR-/- mice. The indicated that AhR knockout in langerin-expressing cells diminishes epidermal LC while enhances Th2 response in epicutaneous protein sensitization. This study indicated AhR in LC helps dampen Th2 response and supported that natural AhR agonist may resolve atopic dermatitis.

Langerin-specific aryl hydrocarbon deficiency diminishes epidermal Langerhans cells and leads to enhance atopic Th2 responses