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Galectin-3 interacts with PD-1 and counteracts the PD-1 pathway-driven regulation of T cell and osteoclast activity in Rheumatoid Arthritis

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Item Type:Article
Title:Galectin-3 interacts with PD-1 and counteracts the PD-1 pathway-driven regulation of T cell and osteoclast activity in Rheumatoid Arthritis
Creators Name:Pedersen, K. and Nielsen, M.A. and Juul-Madsen, K. and Hvid, M. and Deleuran, B. and Greisen, S.R.
Abstract:OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and bone erosions. The glycosylated programmed death-1 (PD-1) receptor plays an important role in regulating immune responses and maintaining tolerance. In this study, we focus on two features observed in RA: impaired PD-1 signaling, and Galectin-3 (Gal-3) upregulation. We hypothesize that Gal-3 binds PD-1 and PD-1 ligands, potentially contributing to impaired PD-1 signaling. METHODS: PD-1 and Gal-3 levels in RA synovial fluid (SF) and plasma were evaluated by ELISA. PD-1 and Gal-3 interaction was examined by Surface Plasmon Resonance and ELISA. PD-1, PD-L1 and Gal-3 expression on mononuclear cells from SF and peripheral blood as well as fibroblast-like synoviocytes were examined by flow cytometry. Effects of Gal-3 and PD-L1 on osteoclast formation was evaluated by tartrate-resistant acid phosphatase assay. RESULTS: We show that Gal-3 binds PD-1 and PD-L1. Results demonstrated high expression of PD-1 and Gal-3 on mononuclear cells, especially from SF. Gal-3 inhibited PD-1 signaling when PD-L1 was present. Furthermore, a role of Gal-3 in osteoclast formation was observed in vitro, both directly but also through PD-1:PD-L1 inhibition. CONCLUSIONS: Effects of Gal-3 on the PD-1 signaling axis are proposed to be inhibitory, meaning high Gal-3 levels in the complex synovial microenvironment are not desirable in RA. Preventing Gal-3's inhibitory role on PD-1 signaling could therefore be a therapeutic target in RA by affecting inflammatory T cell responses and osteoclasts.
Keywords:Rheumatoid Arthritis, Autoimmunity, Inflammation, Co-Inhibitory Receptors, Galectin-3, PD-1
Source:Scandinavian Journal of Immunology
Page Range:e13245
Date:February 2023
Additional Information:Copyright © 2022 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Scandinavian Foundation for Immunology.
Official Publication:https://doi.org/10.1111/sji.13245
PubMed:View item in PubMed

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