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Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis
G A Rabinovich1, G Daly, H Dreja
1Immunology Department, Faculty of Chemical Sciences, National University of Córdoba 5000, Argentina.
Abstract:
Galectin-1 (GAL-1), a member of a family of conserved beta-galactoside-binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2-polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1-expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an A(q)-restricted, collagen type 2-specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1-mediated autoimmune disorders.
Insights
Galectin-1 (GAL-1) therapy effectively treated collagen-induced arthritis in mice by reducing inflammation and promoting immune tolerance. This suggests GAL-1
Area of Science:
- Immunology
- Autoimmune Diseases
- Protein Therapeutics
Background:
- Galectin-1 (GAL-1) is a beta-galactoside-binding protein known to induce apoptosis in T cells.
- Autoimmune disorders like rheumatoid arthritis involve aberrant immune responses.
Purpose of the Study:
- To investigate the therapeutic potential and mechanisms of Galectin-1 (GAL-1) in a collagen-induced arthritis mouse model.
- To evaluate GAL-1's ability to modulate immune responses in autoimmune disease.
Main Methods:
- Engineered fibroblasts secreting GAL-1 were injected into mice with induced arthritis.
- Recombinant GAL-1 was administered daily to assess its therapeutic effects.
- Immune responses, cytokine profiles, antibody levels, and T cell apoptosis were analyzed.
Main Results:
- A single injection of GAL-1-secreting fibroblasts abrogated arthritis manifestations.
- Recombinant GAL-1 treatment reduced pro-inflammatory cytokines and IgG levels, skewing the immune response towards Type 2.
- GAL-1 treatment enhanced antigen-induced apoptosis in lymph node cells and inhibited T cell proliferation in vitro.
Conclusions:
- Galectin-1 (GAL-1) demonstrates significant therapeutic efficacy in collagen-induced arthritis.
- Its immunomodulatory effects, including apoptosis induction and cytokine profile alteration, support its potential for treating autoimmune diseases.
- GAL-1 shows promise as a treatment for T helper cell type 1-mediated autoimmune disorders.