Preclinical characterisation of the GM-CSF receptor as a therapeutic target in rheumatoid arthritis.

Objective: Previous work has suggested that the granulocyte macrophage colony stimulating factor (GM-CSF)-GM-CSF receptor α axis (GM-CSFRα) may provide a new therapeutic target for the treatment of rheumatoid arthritis (RA). Therefore, we investigated the cellular expression of GM-CSFRα in RA synovial tissue and investigated the effects of anti-GM-CSFRα antibody treatment in vitro and in vivo in a preclinical model of RA.

Methods: We compared GM-CSFRα expression on macrophages positive for CD68 or CD163 on synovial biopsy samples from patients with RA or psoriatic arthritis (PsA) to disease controls.

A small-molecule macrophage migration inhibitory factor antagonist protects against glomerulonephritis in lupus-prone NZB/NZW F1 and MRL/lpr mice.

Autoimmunity leads to the activation of innate effector pathways, proinflammatory cytokine production, and end-organ injury. Macrophage migration inhibitory factor (MIF) is an upstream activator of the innate response that mediates the recruitment and retention of monocytes via CD74 and associated chemokine receptors, and it has a role in the maintenance of B lymphocytes. High-expression MIF alleles also are associated with end-organ damage in different autoimmune diseases.

Autoimmune diseases: MIF as a therapeutic target.

Importance Of The Field: Autoimmune inflammatory diseases occur commonly in developed countries. The treatment of these diseases is usually non-curative and is aimed at suppressing inflammatory end-organ damage. Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that has been implicated in the pathogenesis of numerous autoimmune inflammatory disorders.