title: Involvement of the TNF-α/TGF-β/IDO axis in IVIg-induced immune tolerance.
abstract: 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.
authors.affiliation: Department of Research and Development, Héma-Québec, Québec (Qc), Canada.
authors.forename: Lionel
authors.initials: L
authors.lastname: Loubaki
authors.affiliation: Department of Research and Development, Héma-Québec, Québec (Qc), Canada; Department of Biochemistry, Microbiology and Bioinformatics, Laval University, Québec (Qc), Canada.
authors.forename: Dominique
authors.initials: D
authors.lastname: Chabot
authors.affiliation: Department of Research and Development, Héma-Québec, Québec (Qc), Canada; Department of Biochemistry, Microbiology and Bioinformatics, Laval University, Québec (Qc), Canada. Electronic address: renee.bazin@hema-quebec.qc.ca.
authors.forename: Renée
authors.initials: R
authors.lastname: Bazin
mesh_terms: D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D016756:Immunoglobulins, Intravenous; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha
keywords: IDO; Immunomodulation; Intravenous immunoglobulin; TGF-beta; TNF-alpha