Premium
Characterization of psoriasiform dermatitis induced by systemic injection of interleukin‐23 minicircles in mice
Author(s) -
Leys Laura,
Wang Yibing,
Paulsboe Stephanie,
Edelmayer Rebecca,
Salte Katie,
Wetter Joseph,
Namovic Marian,
Phillips Lucy,
Dunstan Robert,
Gauvin Donna,
DonnellyRoberts Diana,
Su Zhi,
Honore Prisca,
McGaraughty Steve
Publication year - 2019
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.14899
Subject(s) - inflammation , immunology , medicine , psoriasis , chemokine , interleukin , pathogenesis , flow cytometry , systemic administration , tumor necrosis factor alpha , cytokine , pharmacology , pathology , biology , in vivo , microbiology and biotechnology
The interleukin ( IL )‐23/ IL ‐17 axis plays a central role in the pathogenesis of psoriasis and is elevated in lesional psoriatic skin. Different murine models have been developed to mimic this pathophysiology each carrying specific merits and limitations. In an attempt to address some of these limitations, B10. RIII mice received a single hydrodynamic injection of IL ‐23 minicircles ( MC ) to induce hepatic transcription and the endogenous production of IL ‐23. Plasma and ear IL ‐23 levels were dose‐dependently (0.3–3 μg) increased in MC injected mice and were sustained over the 14‐day study duration. Beginning on day 7 post‐injection, mice developed dose‐related ear inflammation, histologically confirmed increases in epidermal and dermal area, as well as enhanced neutrophil and macrophage content. Flow cytometry demonstrated increased levels of granulocytes, T cells and monocytes/macrophages in the ear skin, with T cells identified as the main cellular source of IL ‐17A. Evaluation of mRNA and protein showed time‐dependent, increased levels of the IL ‐23/ IL ‐17 pathway and inflammatory/microbial cytokines/chemokines in the ear which differed kinetically from circulating levels. An anti‐ IL ‐23p40 antibody was assessed following both prophylactic administration and administration once the disease was established. Prophylactic dosing completely prevented the development of the ear phenotype across endpoints. Treatment administration showed a dose‐related response, with a maximum inhibition of 64–94%, depending on endpoint. These data demonstrate that the IL ‐23 MC model is a useful approach to study IL ‐23/ IL ‐17‐driven skin inflammation and may facilitate preclinical assessment of novel therapies.