NR4A3 deficiency ameliorates contact hypersensitivity and exacerbates psoriasis by regulating gene expression in dendritic cells

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Abstract NR4A3 is a transcription factor that belongs to the nuclear receptor superfamily. To reveal the roles of NR4A3 in skin diseases, we constructed contact hypersensitivity (CHS)- and imiquimod-induced psoriasis models in Nr4a3 -/- mice. In the CHS induced Nr4a3 -/- mice, ear swelling was significantly reduced, accompanied by suppressed migration of dendritic cells (DCs), in which CCR7 expression was reduced. In contrast, ear swelling in psoriasis model Nr4a3 -/- mice was enhanced. The expression levels of inflammatory cytokines in psoriasis skin lesions and in TLR7-ligand-stimulated DCs were increased by NR4A3 deficiency. Subcutaneous (s.c.) injection of hapten-treated Nr4a3 +/+ DCs induced ear swelling in Nr4a3 -/- mice, and s.c. injection of TLR7-ligand-stimulated Nr4a3 -/- DCs caused significant ear swelling. Compared with Nr4a3 +/+ DCs, Nr4a3 -/- DCs expressed lower levels of CCR7 and IRF4, and higher levels of TLR7, IRF7, IFN-β, and PU.1. Taken together, NR4A3 deficiency ameliorates CHS and exacerbates psoriasis by regulating the expression of CCR7, TLR7, and related transcription factors in DCs.

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