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Updated: Jun 8, 2026
High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Role of differential expression of interferon receptor isoforms on the response of multiple sclerosis patients to
1SCDO Neurology 2-Regional Reference Centre for Multiple Sclerosis (CReSM), Neuroscience Institute of the Cavalieri Ottolenghi Foundation, University Hospital S. Luigi Gonzaga, Ottolenghi, Orbassano (Torino), Italy. francesca.gilli@fastwebnet.it
The cytokine interferon (IFN)-β is successfully used in the treatment of multiple sclerosis. However, some patients fail to respond to therapy, probably due to different biological patterns that are of importance in influencing clinical response. A common mechanism involved in the modulation of responsiveness to cytokine is represented by regulation of their receptor expression through autocrine-ligand-mediated loops. Mechanistically, IFN-β exerts its biological effects through interaction with the IFN-α/-β-receptor (IFNAR), which then activates several transcription factors. IFNAR is composed of 2 chains, IFNAR-1 and IFNAR-2, which associate with IFN-β to form a ternary complex. The major ligand-binding subunit is IFNAR-2 and it exists in 3 mRNA splice variants, resulting in 2 transmembrane (IFNAR-2b and IFNAR-2c) isoforms and a soluble (IFNAR-2a) one. On the contrary, from normal cells only one IFNAR-1 isoform, with transcriptional capacity, was identified. In the past decades, considerable information has accumulated pertaining to the downregulation of the IFNAR complex in IFN-treated patients, but only a few studies have investigated the molecular events involved in this phenomenon. The intent of the present review is to place this receptor downregulation in the context of IFN-β therapy and of its clinical and biological outcomes in IFN-β-treated patients.
The cytokine interferon (IFN)-β is successfully used in the treatment of multiple sclerosis. However, some patients fail to respond to therapy, probably due to different biological patterns that are of importance in influencing clinical response. A common mechanism involved in the modulation of responsiveness to cytokine is represented by regulation of their receptor expression through autocrine-ligand-mediated loops. Mechanistically, IFN-β exerts its biological effects through interaction with the IFN-α/-β-receptor (IFNAR), which then activates several transcription factors. IFNAR is composed of 2 chains, IFNAR-1 and IFNAR-2, which associate with IFN-β to form a ternary complex. The major ligand-binding subunit is IFNAR-2 and it exists in 3 mRNA splice variants, resulting in 2 transmembrane (IFNAR-2b and IFNAR-2c) isoforms and a soluble (IFNAR-2a) one. On the contrary, from normal cells only one IFNAR-1 isoform, with transcriptional capacity, was identified. In the past decades, considerable information has accumulated pertaining to the downregulation of the IFNAR complex in IFN-treated patients, but only a few studies have investigated the molecular events involved in this phenomenon. The intent of the present review is to place this receptor downregulation in the context of IFN-β therapy and of its clinical and biological outcomes in IFN-β-treated patients.
