Galectin-3-anchored indoleamine 2,3-dioxygenase ameliorates imiquimod-induced psoriasis-like dermatitis via remodeling of inflammatory and fibrotic programs

Localized anti-inflammatory treatment options for psoriasis are limited. In a murine model of imiquimod-induced psoriasis, subcutaneous administration of a protein created by the fusion of indoleamine 2,3-dioxygenase and galectin-3 (IDO-Gal3) was investigated. Prior work has established that fusion with Gal3 provides localized tissue retention of IDO, avoiding systemic distribution of the protein and affords dose sparing. A single subcutaneous administration at the time of psoriasis onset remarkably decreased disease severity, quantified using the psoriasis area and severity index (PASI) metrics of skin redness, scaling and thickening. Infiltrating immune cells, particularly neutrophils, macrophages, and gamma delta T cells and inflammatory responses were significantly reduced. Transcriptomic analyses indicate inflammation and fibrosis-associated programs were also substantially reduced following IDO-Gal3 treatment. These data demonstrate IDO-Gal3 treatment ameliorates psoriasis with concomitant remodeling of inflammatory and fibrotic programs.