Conference Agenda

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting ~1% of the global population, with current therapies largely limited to symptom control and are associated with adverse effects. There is an urgent need for novel treatments targeting underlying disease mechanisms. Hookworms secrete immunomodulatory proteins that have evolved to regulate host immunity.

Here, we investigate a recombinant fatty acid- and retinol-binding protein, Ac-FAR-2, derived from the secretome of Ancylostoma caninum, as a hookworm-inspired therapeutic candidate for RA. Ac-FAR-2 significantly attenuated disease severity in a murine model of RA, with histological and confocal analyses revealing reduced macrophage infiltration in joint tissues. In vitro, Ac-FAR-2 suppressed inflammatory cytokine production in human peripheral blood mononuclear cells and THP-1-derived macrophages. This effect was associated with reduced co-stimulatory marker expression and impaired T-cell proliferation in co-culture systems.

Mechanistically, Ac-FAR-2 interacted with macrophage surface molecules and disrupted the arachidonic acid–prostaglandin E2 pathway. Transcriptomic profiling further demonstrated downregulation of NF-κB signaling, inflammasome-related genes, and other pro-inflammatory pathways in LPS-stimulated human macrophages.

These findings identify Ac-FAR-2 as a promising immunomodulatory candidate for RA and other macrophage-driven autoimmune diseases.