Indoleamine 2,3-dioxygenase-galectin-3 fusion protein remodels inflammatory and fibrotic programs, ameliorating...

Localized anti-inflammatory treatment options for psoriasis are limited. Addressing this, a fusion protein was created consisting of the regulatory enzyme indoleamine 2,3-dioxygenase (IDO) fused to carbohydrate-binding protein galectin-3 (Gal3), termed IDO-Gal3, and therapeutic potential was investigated in a murine model of imiquimod-induced psoriasis. Prior work established that Gal3 fusion provides prolonged localized tissue retention of injected fusion protein, which colocalizes therapeutic to the site of inflammation, limits systemic distribution, and reduces potential for off-target side-effects. A single subcutaneous administration at disease onset remarkably decreased the disease metrics of skin redness, scaling and thickening, as measured by the psoriasis area and severity index (PASI) composite score. Infiltrating immune cells, particularly neutrophils and gamma delta T cells, and inflammatory responses were significantly reduced. Transcriptomic analyses indicated inflammation and fibrosis-associated programs were also substantially reduced following IDO-Gal3 treatment. These data demonstrate IDO-Gal3 treatment ameliorated psoriasis with concomitant remodeling of inflammatory and fibrotic programs.