Abstract
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.
Highlights
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints
These results suggest that endogenous BTN2A2 is an integral cell surface protein that is expressed on resting and activated T cells, dendritic cells (DCs), macrophages and B cells
We have shown here that BTN2A2 is expressed on dendritic cells, macrophages and B cells, and its expression levels were significantly upregulated upon activation
Summary
Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)induced arthritis (CIA) is the most used animal model for human RA. BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models. Collagen-induced arthritis (CIA) is a wellcharacterized mouse model for human RA, in which injection of type II collagen (CII) into male DBA/1 mice induces swelling and progressive inflammation in joints, leading to arthritis. Btn2a2-deficient mice have enhanced effector CD4+ and CD8+ T cell responses, impaired CD4+ regulatory T cell induction, and exacerbated experimental autoimmune encephalomyelitis[8]
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