Nature biomedical engineering · 2023
Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.
СтатьяПоддержка NIH: внешняя программаПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Bracho-Sanchez Evelyn, Rocha Fernanda G, Bedingfield Sean K, Partain Brittany D, Macias Sabrina L, Brusko Maigan A, Colazo Juan M, Fettis Margaret M, Farhadi Shaheen A, Helm Eric Y, Koenders Kevin, Kwiatkowski Alexander J, Restuccia Antonietta, Morales Bethsymarie Soto, Wanchoo Arun, Avram Dorina, Allen Kyle D, Duvall Craig L, Wallet Shannon M, Hudalla Gregory A, Keselowsky Benjamin G
Аннотация
The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site. In rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis, the fusion protein remained in the inflamed tissues and joints for about 1 week after injection, and the amelioration of local inflammation, disease progression and inflammatory pain in the animals were concomitant with homoeostatic preservation of the tissues and with the absence of global immune suppression. IDO-Gal3 may serve as an immunomodulatory enzyme for the control of focal inflammation in other inflammatory conditions.