974 Decreased epidermal thickening by imiquimod in mice with conditional aryl hydrocarbon receptor ablation in langerhans cells: A potential role of autophagy by dysregulated AhR activation in psoriasis

Psoriasis is a common inflammatory skin disease with aberrant Th17 polarization. Aryl hydrocarbon receptor (AhR), an environmental sensor, dysregulated in psoriasis and AhR controls differentiation. Targeting by Tapinarof effective for treating psoriasis. Langerhans cells (LC) are immediate targets of exogenous ligands. However, how LC contributes to remains largely undetermined. Our previous study showed conditional ablation LC, decreases while induces Th2/Tr1 The current measured expression human correlated that clinical severity. langerin-specific knockout (Langerin-AhR-/-) mice were established tested imiquimod induced immunofluorescent exam numbers CD207-expressing decreased negatively associated While the epidermal does not differ significantly psoriatic than normal skin, most localized cytosol. In CD207 colocalized LC3b, marker autophagy. mice, thickening was attenuated Langerin-AhR-/- mice. Flow cytometry consistently imiquimod-induced Activation ITE bone marrow derived Langerhans-like (BMLC), did affect their activation markers, including CD80, CD86, MHC2. immunoblotting immunofluorescence increased early beclin-1, inhibition CH223191 led late induction LC3b p62, indicating regulates autophagy LC. This aryl cells. Autophagy may contribute development