Format

Send to

Choose Destination
J Invest Dermatol. 2018 Nov 10. pii: S0022-202X(18)32806-9. doi: 10.1016/j.jid.2018.09.037. [Epub ahead of print]

Biological effects of IL-26 on T cell-mediated skin inflammation including psoriasis.

Author information

1
Graduate School of Health and Sports Science, Juntendo University, 1-1, Hirakagakuendai, Inzai, Chiba 270-1695, Japan.
2
Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
3
Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan; Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Tomioka, Urayasu, Chiba 279-0021, Japan.
4
Department of Medicine, Vanderbilt University School of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, U.S.A.
5
Division of Hematology/Oncology, University of Florida, 1600 SW Archer Road-Box 100278, Room MSB M410A, Gainesville, FL 32610, U.S.A.
6
Department of Immunological Diagnosis, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
7
Institute for Environmental and Gender Specific Medicine, Juntendo University Graduate School of Medicine, 2-1-1, Tomioka, Urayasu, Chiba 279-0021, Japan.
8
Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address: kohnuma@juntendo.ac.jp.

Abstract

Psoriasis is a chronic inflammatory skin disease mainly characterized by epidermal hyperplasia, scaling and erythema, with Th17 cells having a role in its pathogenesis. Although IL-26, known as a Th17 cytokine, is upregulated in psoriatic skin lesions, its precise role is unclear. We now investigate the role of IL-26 in the imiquimod (IMQ)-induced psoriasis-like murine model using human IL-26 transgenic (hIL-26Tg) mice. Erythema symptoms induced by daily applications of IMQ dramatically increased in hIL-26Tg mice as compared with controls. Vascularization and immune cell infiltration were prominent in skin lesions of hIL-26Tg mice. Levels of fibroblast growth factor (FGF)-1, FGF2 and FGF7 were significantly upregulated in the skin lesions of IMQ-treated hIL-26Tg mice and psoriasis patients. In vitro analysis demonstrated that FGF1, FGF2 and FGF7 levels were elevated in human keratinocytes and vascular endothelial cells following IL-26 stimulation. Furthermore, IL-26 directly acted on vascular endothelial cells, promoting proliferation and tube formation, possibly through Akt, ERK and NF-kB pathways. Moreover, similar effects of IL-26 were observed in the murine contact hypersensitivity model, indicating that these effects are not restricted to psoriasis. Altogether, our data indicate that IL-26 may be a promising therapeutic target in T cell-mediated skin inflammation including psoriasis.

KEYWORDS:

angiogenesis; fibroblast growth factors; imiquimod; interleukin-26; psoriasis

PMID:
30423328
DOI:
10.1016/j.jid.2018.09.037

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center