Fingolimod ameliorates imiquimod-induced psoriasiform dermatitis by sequestrating interleukin-17-producing ?d T cells in secondary lymph nodes.

Abstract

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.

• Authors: Iori Okura, Masahiro Kamata, Yoshihide Asano, Aya Mitsui, Teruo Shimizu, Shinichi Sato, Yayoi Tada
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 102 Issue 2 Pg. 116-125 (May 2021) ISSN: 1873-569X [Electronic] Netherlands
• PMID: 33888401 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Interleukin-17
• Fingolimod Hydrochloride
• Imiquimod

Topics

• Animals
• Disease Models, Animal
• Down-Regulation (drug effects, immunology)
• Drug Evaluation, Preclinical
• Female
• Fingolimod Hydrochloride (pharmacology, therapeutic use)
• Humans
• Imiquimod (administration & dosage, immunology)
• Interleukin-17 (metabolism)
• Intraepithelial Lymphocytes (drug effects, immunology, metabolism)
• Langerhans Cells (immunology, metabolism)
• Lymph Nodes (cytology, drug effects, immunology, metabolism)
• Mice
• Psoriasis (drug therapy, immunology, pathology)
• Skin (cytology, drug effects, immunology, metabolism)
• Up-Regulation (drug effects, immunology)