Suppression of local inflammation via galectin-anchored indoleamine 2,3-dioxygenase
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 01, 2023
- Source ID
- 10.1038/s41551-023-01025-1
Entities
People
- Alexander J. Kwiatkowski
- Antonietta Restuccia
- Arun Wanchoo
- Benjamin G Keselowsky
- Bethsymarie Soto Morales
- Brittany D. Partain
- Craig Duvall
- Dorina Avram
- Eric Y. Helm
- Evelyn Bracho-sanchez
- Fernanda G. Rocha
- Gregory A Hudalla
- Juan Colazo
- Kevin Koenders
- Kyle D. Allen
- Maigan A. Brusko
- Margaret M. Fettis
- Sabrina L. Macias
- Sean K. Bedingfield
- Shaheen A. Farhadi
- Shannon M. Wallet
Organizations
- Congressionally Directed Medical Research Programs
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- Division of Materials Research
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of Dental and Craniofacial Research
- National Institute of General Medical Sciences