Fingolimod ameliorates imiquimod-induced psoriasiform dermatitis by sequestrating interleukin-17-producing ?d T cells in secondary lymph nodes
| Autor: | Aya Mitsui, Teruo Shimizu, Yayoi Tada, Shinichi Sato, Iori Okura, Yoshihide Asano, Masahiro Kamata |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Drug Evaluation Preclinical Down-Regulation Imiquimod Dermatology Biochemistry Mice 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Psoriasis medicine Animals Humans Intraepithelial Lymphocytes Molecular Biology Psoriasiform Dermatitis Lymph node Skin integumentary system Fingolimod Hydrochloride business.industry Interleukin-17 Interleukin medicine.disease Fingolimod Up-Regulation Disease Models Animal 030104 developmental biology medicine.anatomical_structure Langerhans Cells Immunology Female Lymph Nodes Interleukin 17 Lymph business medicine.drug |
| Zdroj: | Journal of Dermatological Science. 102:116-125 |
| ISSN: | 0923-1811 |
| DOI: | 10.1016/j.jdermsci.2021.04.004 |
| Popis: | Background Psoriasis is a chronic inflammatory skin disease. Interleukin (IL)-17A plays a key role in the pathogenesis of psoriasis. Fingolimod, which is available for the treatment of multiple sclerosis, exerts anti-inflammatory effects by sequestrating inflammatory lymphocytes in secondary lymphoid tissues and the thymus. The effect of fingolimod on psoriasis has not been reported yet. Objective Our objectives were to investigate the effect of fingolimod on psoriasis utilizing mice with imiquimod (IMQ)-induced psoriasiform dermatitis, and explore the possibility of fingolimod as a therapeutic agent for psoriasis. Methods Psoriasiform dermatitis was induced by imiquimod application on murine shaved back skin for six days. Fingolimod prepared in phosphate-buffered saline (PBS), or PBS alone as a control, was administered intraperitoneally daily from days 0 to 5. Results Fingolimod ameliorated IMQ-induced psoriasis dermatitis clinically and histologically. On day 6, the mRNA expression level of IL-17A was lower in the skin of fingolimod-treated mice than in that of PBS-treated mice, whereas it was higher in the inguinal lymph nodes of fingolimod-treated mice than in those of PBS-treated mice. Flow cytometric analyses revealed that fingolimod reduced IL-17A-producing ?d T cells infiltrating into the skin, whereas it increased these cells in the inguinal lymph nodes. Fingolimod inhibited egress of Langerhans cells from the skin to lymph nodes. Conclusion Our results demonstrated that fingolimod showed effectiveness for IMQ-induced psoriasiform dermatitis by hindering the emigration of IL-17A-producing ?d T cells from the lymph nodes to the skin, and suggest that fingolimod is a promising candidate for the treatment of psoriasis. |
| Databáze: | OpenAIRE |
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