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Skin-penetrating methotrexate alleviates imiquimod-induced psoriasiform dermatitis via decreasing IL-17-producing gamma delta T cells

Authors
 Dashlkhumbe Byamba  ;  Do Young Kim  ;  Dae-Suk Kim  ;  Tae-Gyun Kim  ;  Hyunjoong Jee  ;  Sung Hee Kim  ;  Tae-Yoon Park  ;  Sang-Hwa Yang  ;  Sang-Kyou Lee  ;  Min-Geol Lee 
Citation
 EXPERIMENTAL DERMATOLOGY, Vol.23(7) : 492-496, 2014 
Journal Title
 EXPERIMENTAL DERMATOLOGY 
ISSN
 0906-6705 
Issue Date
2014
MeSH
Aminoquinolines/adverse effects ; Animals ; CD11c Antigen/metabolism ; CD4-Positive T-Lymphocytes/cytology ; Cytokines/metabolism ; DNA, Complementary/metabolism ; Dermatitis/drug therapy* ; Dermatitis/etiology ; Female ; Inflammation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism ; Methotrexate/administration & dosage* ; Mice ; Mice, Inbred BALB C ; Peptides/chemistry ; Permeability ; Psoriasis/chemically induced ; Psoriasis/drug therapy* ; Psoriasis/immunology ; Skin/drug effects* ; Skin/immunology ; Skin/pathology
Keywords
imiquimod ; methotrexate ; protein transduction domain ; psoriasis
Abstract
Accumulating evidence has shown that the Toll-like receptor 7 agonist imiquimod (IMQ) induces psoriasiform skin inflammation in mice and that this inflammation is dependent on the IL-23/IL-17 axis. Moreover, it has been demonstrated that the main source of IL-17 is not Th17 but is dermal gamma delta (γδ) T cells in mouse psoriasiform skin. Recent advances in the understanding of immunopathogenesis of psoriasis led to an alteration in the treatment paradigm to the use of highly efficacious biologics. However, their high cost impedes the extensive use of these agents. Thus, inexpensive and safe medications are still considered valuable. In this study, we introduce the therapeutic efficacy of a newly formulated methotrexate (MTX), a chemical conjugate of MTX with cell permeable peptide, for the treatment of psoriasis. Topically applied skin-penetrating (SP)-MTX reduced the psoriasiform skin phenomenon, epidermal thickness and infiltrating immune cells into the dermis. IL-17A-producing dermal γδ T cells in the cellular infiltrate that contribute IL-23/IL-17 axis were well abrogated by SP-MTX. Furthermore, SP-MTX had no toxic effects on liver, kidney or myeloid cells, unlike systemic administration of MTX. In conclusion, topically applied SP-MTX ameliorated psoriasiform skin inflammation in mice with the criteria of clinical phenomenon, histopathology and immunology, without inducing systemic toxic effects.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/exd.12448/abstract
DOI
10.1111/exd.12448
Appears in Collections:
5. Research Institutes (연구소) > Cancer Metastasis Research Center (암전이연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dae Suk(김대석)
Kim, Do Young(김도영) ORCID logo https://orcid.org/0000-0002-0194-9854
Kim, Sung Hee(김성희)
Kim, Tae-Gyun(김태균) ORCID logo https://orcid.org/0000-0002-2116-4579
Yang, Sang Hwa(양상화)
Lee, Min Geol(이민걸) ORCID logo https://orcid.org/0000-0001-7040-5335
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99488
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