Essential Role of CARD14 in Murine Experimental Psoriasis
| Autor: | Ken Ishii, Kenji Kabashima, Kenji Mizuguchi, Kozue Uchio-Yamada, Kouji Kobiyama, Yayoi Natsume-Kitatani, Mayuri Tanaka, Tetsuya Honda |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
T-Lymphocytes Immunology Inflammation Interleukin-23 Mice 03 medical and health sciences Chimera (genetics) 0302 clinical medicine Dermis Psoriasis medicine Animals Humans Immunology and Allergy Molecular Targeted Therapy Caspase Skin Mice Knockout Imiquimod Membrane Glycoproteins biology Chimera Interleukins Interleukin-17 TLR9 TLR7 medicine.disease CARD Signaling Adaptor Proteins Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Toll-Like Receptor 7 Langerhans Cells Toll-Like Receptor 9 Models Animal Aminoquinolines biology.protein Bone marrow medicine.symptom Transcriptome Guanylate Kinases 030215 immunology |
| Zdroj: | The Journal of Immunology. 200:71-81 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1700995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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