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

Katagiri, M.; Ito, N.; Nagata, K.; Nakano, S.; Minamikawa, N.; Yamashita, N.; Takahashi, M.; Kurihara, M.; Nagaoka, M.; Ando, M.; Ito, T.; Yashiro, T.; Yoshimura, A.; Nishiyama, C.

doi:10.1101/2024.02.20.581116

bioRxiv · 10.1101/2024.02.20.581116

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

Katagiri, M.·Ito, N.·Nagata, K.·Nakano, S.·Minamikawa, N.·Yamashita, N.·Takahashi, M.·Kurihara, M.·Nagaoka, M.·Ando, M.·Ito, T.·Yashiro, T.·Yoshimura, A.·Nishiyama, C.

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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-{beta}, 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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Katagiri, M., Ito, N., Nagata, K., Nakano, S., Minamikawa, N., Yamashita, N., Takahashi, M., Kurihara, M., Nagaoka, M., Ando, M., Ito, T., Yashiro, T., Yoshimura, A., Nishiyama, C.. 2024-02-21. NR4A3 deficiency ameliorates contact hypersensitivity and exacerbates psoriasis by regulating gene expression in dendritic cells. https://doi.org/10.1101/2024.02.20.581116

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