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

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, Mingeol Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)492-496
Number of pages5
JournalExperimental Dermatology
Volume23
Issue number7
DOIs
Publication statusPublished - 2014 Jan 1

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imiquimod
Dermatitis
Somatostatin-Secreting Cells
T-cells
Interleukin-17
Methotrexate
Skin
T-Lymphocytes
Interleukin-23
Poisons
Inflammation
Psoriasis
Toll-Like Receptor 7
Immunology
Biological Products
Liver
Myeloid Cells
Dermis
Allergy and Immunology

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Byamba, Dashlkhumbe ; Kim, Do Young ; Kim, Dae Suk ; Kim, Tae Gyun ; Jee, Hyunjoong ; Kim, Sung Hee ; Park, Tae Yoon ; Yang, Sang Hwa ; Lee, Sang Kyou ; Lee, Mingeol. / Skin-penetrating methotrexate alleviates imiquimod-induced psoriasiform dermatitis via decreasing IL-17-producing gamma delta T cells. In: Experimental Dermatology. 2014 ; Vol. 23, No. 7. pp. 492-496.
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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.",
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Skin-penetrating methotrexate alleviates imiquimod-induced psoriasiform dermatitis via decreasing IL-17-producing gamma delta T cells. / Byamba, Dashlkhumbe; Kim, Do Young; Kim, Dae Suk; Kim, Tae Gyun; Jee, Hyunjoong; Kim, Sung Hee; Park, Tae Yoon; Yang, Sang Hwa; Lee, Sang Kyou; Lee, Mingeol.

In: Experimental Dermatology, Vol. 23, No. 7, 01.01.2014, p. 492-496.

Research output: Contribution to journalArticle

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AU - Byamba, Dashlkhumbe

AU - Kim, Do Young

AU - Kim, Dae Suk

AU - Kim, Tae Gyun

AU - Jee, Hyunjoong

AU - Kim, Sung Hee

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AU - Yang, Sang Hwa

AU - Lee, Sang Kyou

AU - Lee, Mingeol

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