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Papers of the Week

Papers: 29 Apr 2023 - 5 May 2023


Animal Studies, Molecular/Cellular, Neurobiology, Pharmacology/Drug Development


2023 May 01

Nat Biomed Eng


Editor's Pick

Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase.


Bracho-Sanchez E, Rocha FG, Bedingfield SK, Partain BD, Macias SL, Brusko MA, Colazo JM, Fettis MM, Farhadi SA, Helm EY, Koenders K, Kwiatkowski AJ, Restuccia A, Morales BS, Wanchoo A, Avram D, Allen KD, Duvall CL, Wallet SM, Hudalla GA, Keselowsky BG


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.