Involvement of the TNF-α/TGF-β/IDO axis in IVIg-induced immune tolerance

•IVIg stimulates the expression of TGF-β.•TNF-α and its cognate receptors (TNF-R1 and TNF-R2) are increased by IVIg treatment.•IDO expression but not activity is augmented in IVIg-treated monocytes.•IVIg-induced immune tolerance may involve the TNF-α/TGF-β/IDO axis.

The immune tolerance induced by IVIg treatment is generally attributed to its capacity to modulate the functions of antigen presenting cells and to induce the expansion of regulatory T cells by mechanisms that are not well-defined. Herein, we investigated the contribution of the TNF-α/TGF-β/IDO axis to IVIg-induced immune tolerance. We show that high dose IVIg is able to markedly increase the expression (>3 fold) of the well-known tolerogenic cytokine TGF-β in monocytes. In addition, the expression of TNF-α, a pleiotropic cytokine that controls TGF-β-induced tolerogenic effects, as well as of its cognate receptors (TNF-R1 and TNF-R2) is also significantly increased following IVIg treatment. Along with TNF-α, the expression of the enzyme and signaling protein IDO, known to mediate TGF-β dependant tolerogenic effect, is similarly increased following IVIg treatment. We thus propose that the complex interplay between plasticity of immune cells and environmental modifications in which the TNF-α/TGF-β/IDO axis may represent a new mechanism contributing to the development of tolerance in IVIg-treated patients.