Development of a Nascent Galectin-1 Chimeric Molecule for Studying the Role of Leukocyte Galectin-1 Ligands and Immune Disease Modulation
- 15 October 2010
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 185 (8), 4659-4672
- https://doi.org/10.4049/jimmunol.1000715
Abstract
Galectin-1 (Gal-1), a β-galactoside–binding lectin, plays a profound role in modulating adaptive immune responses by altering the phenotype and fate of T cells. Experimental data showing recombinant Gal-1 (rGal-1) efficacy on T cell viability and cytokine production, nevertheless, is controversial due to the necessity of using stabilizing chemicals to help retain Gal-1 structure and function. To address this drawback, we developed a mouse Gal-1 human Ig chimera (Gal-1hFc) that did not need chemical stabilization for Gal-1 ligand recognition, apoptosis induction, and cytokine modulation in a variety of leukocyte models. At high concentrations, Gal-1hFc induced apoptosis in Gal-1 ligand+ Th1 and Th17 cells, leukemic cells, and granulocytes from synovial fluids of patients with rheumatoid arthritis. Importantly, at low, more physiologic concentrations, Gal-1hFc retained its homodimeric form without losing functionality. Not only did Gal-1hFc–binding trigger IL-10 and Th2 cytokine expression in activated T cells, but members of the CD28 family and several other immunomodulatory molecules were upregulated. In a mouse model of contact hypersensitivity, we found that a non-Fc receptor-binding isoform of Gal-1hFc, Gal-1hFc2, alleviated T cell-dependent inflammation by increasing IL-4+, IL-10+, TGF-β+, and CD25high/FoxP3+ T cells, and by decreasing IFN-γ+ and IL-17+ T cells. Moreover, in human skin-resident T cell cultures, Gal-1hFc diminished IL-17+ T cells and increased IL-4+ and IL-10+ T cells. Gal-1hFc will not only be a useful new tool for investigating the role of Gal-1 ligands in leukocyte death and cytokine stimulation, but for studying how Gal-1–Gal-1 ligand binding shapes the intensity of immune responses.Keywords
This publication has 55 references indexed in Scilit:
- Alpha 1,3 fucosyltransferases are master regulators of prostate cancer cell traffickingProceedings of the National Academy of Sciences of the United States of America, 2009
- Intravenous immunoglobulin contains a broad repertoire of anticarbohydrate antibodies that is not restricted to the IgG2 subclassJournal of Allergy and Clinical Immunology, 2009
- Galectin-1 Induces Reversible Phosphatidylserine Exposure at the Plasma MembraneMolecular Biology of the Cell, 2009
- Ligand Reduces Galectin-1 Sensitivity to Oxidative Inactivation by Enhancing Dimer Formation*Journal of Biological Chemistry, 2009
- Critical Role of the Solvent Environment in Galectin-1 Binding to the Disaccharide LactoseBiochemistry, 2009
- Galectin‐1 functions as a Th2 cytokine that selectively induces Th1 apoptosis and promotes Th2 functionEuropean Journal of Immunology, 2008
- Galectin-1 signaling in leukocytes requires expression of complex-type N-glycansGlycobiology, 2008
- The AP1-dependent secretion of galectin-1 by Reed–Sternberg cells fosters immune privilege in classical Hodgkin lymphomaProceedings of the National Academy of Sciences of the United States of America, 2007
- IL-15 and dermal fibroblasts induce proliferation of natural regulatory T cells isolated from human skinBlood, 2006
- The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritisArthritis & Rheumatism, 1988