IDO-expressing Fibroblasts Suppress the Development of Imiquimod-induced Psoriasis-like Dermatitis

• Published in: Cell transplantation Vol. 27; no. 3; pp. 557 - 570
• Main Authors: Elizei, Sanam Salimi, Pakyari, Mohammadreza, Ghoreishi, Mehraneh, Kilani, Ruhangiz, Mahmoudi, Sanaz, Ghahary, Aziz
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-03-2018; Sage Publications Ltd; SAGE Publishing
• Subjects: Animals; Antiviral drugs; CD4 antigen; Cytokines; Dendritic cells; Dermatitis; Dermatitis - therapy; Ear; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - physiology; Flow Cytometry; Imiquimod; Imiquimod - toxicity; Immunohistochemistry; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Interleukin 17; Interleukin 23; Interleukin-17 - metabolism; Interleukin-23 - metabolism; Leukocytes (granulocytic); Lymphocytes T; Macrophages; Mice; Mice, Inbred BALB C; Original; Psoriasis; Psoriasis - chemically induced; Psoriasis - metabolism; Skin diseases; Tryptophan 2,3-dioxygenase; fibroblasts; IMQ; IL-23; IDO; psoriasis; IL-17
• ISSN: 0963-6897; 1555-3892
• DOI: 10.1177/0963689718757482

Psoriasis is a chronic skin condition whose pathogenesis is reported to be due to the activation of the interleukin-23/interleukin-17 (IL-23/IL-17) pathway. Here, we report that indoleamine 2,3-dioxygenase (IDO)-expressing fibroblasts reduce the activity of this pathway in activated immune cells. The findings showed that intralesional injection of IDO-expressing fibroblasts in imiquimod-induced psoriasis-like dermatitis on the back and ear (Pso. ear group) in mice significantly improves the clinical lesional appearance by reducing the number of skin-infiltrated IL-17+ CD4+ T cells (1.9% ± 0.3% vs. 6.9% ± 0.6%, n = 3, P value < 0.01), IL-17+ γδ+ T cells (2.8% ± 0.3% vs. 11.6% ± 1.2%, n = 3, P value < 0.01), IL-23+ activated dendritic cells (7.6% ± 0.9% vs. 14.0% ± 0.5%, n = 3, P < 0.01), macrophages (4.3% ± 0.1% vs. 11.3% ± 1.0%, n = 3, P value < 0.01), and granulocytes (2.5% ± 0.4% vs. 4.5% ± 0.3%, n = 3, P value < 0.01) as compared to untreated psoriatic mice. This finding suggests that IDO-expressing fibroblasts, and to a lesser extent, non-IDO primary fibroblasts suppress the psoriatic-like symptoms by inhibiting the infiltration of key immune cells involved in the development of psoriasis.