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Mechanobiology

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

AUTHORS

Bracho-Sanchez EEvelyn , Rocha FGFernanda G , Bedingfield SKSean K , Partain BDBrittany D , Macias SLSabrina L , Brusko MAMaigan A , Colazo JMJuan M , Fettis MMMargaret M , Farhadi SAShaheen A , Helm EYEric Y , Koenders KKevin , Kwiatkowski AJAlexander J , Restuccia AAntonietta , Morales BSBethsymarie Soto , Wanchoo AArun , Avram DDorina , Allen KDKyle D , Duvall CLCraig L , Wallet SMShannon M , Hudalla GAGregory A , Keselowsky BGBenjamin G . Nature biomedical engineering. 2023 05 01; ().

ABSTRACT

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.