Protective effects of agonistic anti-4-1BB antibody on the development of imiquimod-induced psoriasis-like dermatitis in mice.

Abstract

Agonistic anti-4-1BB antibodies (Abs) play a central role in immunomodulatory conditions that control the pathogenesis of immune-mediated autoimmune and allergic diseases. However, the effects of agonistic anti-4-1BB Abs have not been examined in an experimental mouse model of psoriasis. Therefore, we investigated the protective effects of agonistic anti-4-1BB Abs, using imiquimod (IMQ)-induced psoriasis-like dermatitis in mice, a condition histologically and clinically similar to human psoriasis. We found that administration of agonistic anti-4-1BB Abs (10mg/kg) significantly alleviated the severity of IMQ-induced psoriasis-like skin inflammation in mice, with reduced histologic symptoms, including inflammatory infiltration, parakeratosis, and hyperkeratosis. Subsequent analyses revealed that the production of Th17 cytokines (IL-17A and IL-23) in the serum and skin of IMQ-induced mice was significantly inhibited by agonistic anti-4-1BB Abs (10mg/kg), although Th1 cytokines (TNF-α and IFN-γ) were not. Moreover, administration of agonistic anti-4-1BB Abs (10mg/kg) induced a relative increase of CD4(+)FoxP3(+) regulatory T (Treg) cells in the spleen and draining lymph node (DLN). Taken together, our data provide evidence that agonistic anti-4-1BB Abs possesses immunosuppressive properties in IMQ-induced psoriasis-like skin inflammation, providing insight into the immunomodulatory effect of agonistic anti-4-1BB Abs for psoriasis immunotherapy.

• Authors: Jung Ki Yoo, Young-Kug Choo, Dong Hoon Kwak, Jong Min Lee, Chi-Yeon Lim, Ju-Hee Lee, Mi-Young Park, Chang-Hyun Kim
• Journal: Immunology letters (Immunol Lett) Vol. 178 Pg. 131-9 (10 2016) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 27592361 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• Aminoquinolines
• Antibodies, Monoclonal
• Cytokines
• Inflammation Mediators
• Protective Agents
• Tumor Necrosis Factor Receptor Superfamily, Member 9
• Imiquimod

Topics

• Aminoquinolines (adverse effects)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Biopsy
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Imiquimod
• Inflammation Mediators (metabolism)
• Mice
• Phenotype
• Protective Agents (pharmacology)
• Psoriasis (drug therapy, etiology, metabolism, pathology)
• Skin (drug effects, metabolism, pathology)
• Splenomegaly
• T-Lymphocyte Subsets (immunology, metabolism)
• T-Lymphocytes, Regulatory (drug effects, immunology, metabolism)
• Th17 Cells (drug effects, immunology, metabolism)
• Tumor Necrosis Factor Receptor Superfamily, Member 9 (agonists)