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J Immunol. 2018 Jan 1;200(1):71-81. doi: 10.4049/jimmunol.1700995. Epub 2017 Nov 17.

Essential Role of CARD14 in Murine Experimental Psoriasis.

Author information

1
Laboratory of Adjuvant Innovation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
2
Laboratory of Vaccine Science, World Premier International Research Center Initiative Immunology Frontier Research Center, Osaka University, Osaka 567-0871, Japan.
3
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
4
Laboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; and.
5
Laboratory of Bioinformatics, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
6
Laboratory of Adjuvant Innovation, Center for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; kenishii@biken.osaka-u.ac.jp.

Abstract

Caspase recruitment domain family member 14 (CARD14) was recently identified as a psoriasis-susceptibility gene, but its immunological role in the pathogenesis of psoriasis in vivo remains unclear. In this study, we examined the role of CARD14 in murine experimental models of psoriasis induced by either imiquimod (IMQ) cream or recombinant IL-23 injection. In all models tested, the psoriasiform skin inflammation was abrogated in Card14-/- mice. Comparison of the early gene signature of the skin between IMQ-cream-treated Card14-/- mice and Tlr7-/-Tlr9-/- mice revealed not only their similarity, but also distinct gene sets targeted by IL-23. Cell type-specific analysis of these mice identified skin Langerinhigh Langerhans cells as a potent producer of IL-23, which was dependent on both TLR7 and TLR9 but independent of CARD14, suggesting that CARD14 is acting downstream of IL-23, not TLR7 or TLR9. Instead, a bone marrow chimera study suggested that CARD14 in radio-sensitive hematopoietic cells was required for IMQ-induced psoriasiform skin inflammation, controlling the number of Vγ4+ T cells producing IL-17 or IL-22 infiltrating through the dermis to the inflamed epidermis. These data indicate that CARD14 is essential and a potential therapeutic target for psoriasis.

PMID:
29150564
DOI:
10.4049/jimmunol.1700995
[Indexed for MEDLINE]

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