Role of MIF and D-DT in immune-inflammatory, autoimmune, and chronic respiratory diseases: from pathogenic factors to therapeutic targets. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Günther, Sven; Fagone, Paolo; Jalce, Gaël; Atanasov, Atanas G.; Guignabert, Christophe; Nicoletti, Ferdinando
• Is Part Of: Drug discovery today. Volume 24:Issue 2(2019)
• Page Start: 428
• Page End: 439
• Publication Date: 2019-02
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2018.11.003
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: MIF acts cytokine, enzyme, endocrine hormone and chaperon-like molecule. D-DT, a member of the MIF family, exerts non-redundant effects from MIF. MIF and D-DT are up-regulated in immune-inflammatory, and chronic disorders. Inhibition of MIF and/or D-DT may represent a novel therapeutic avenue. Abstract : Macrophage migration inhibitory factor (MIF) is a protein that acts as a cytokine-, enzyme-, endocrine- and chaperon-like molecule. It binds to the cell-surface receptor CD74 in association with CD44, which activates the downstream signal transduction pathway. In addition, MIF acts also as a noncognate ligand for C-X-C chemokine receptor type 2 (CXCR2), type 4 (CXCR4), and type 7 (CXCR7). Recently, D-dopachrome tautomerase (D-DT), a second member of the MIF superfamily, was identified. From a pharmacological and clinical point of view, the nonredundant biological properties of MIF and D-DT anticipate potential synergisms from their simultaneous inhibition. Here, we focus on the role of MIF and D-DT in human immune-inflammatory, autoimmune, and chronic respiratory diseases, providing an update on the progress made in the identification of specific small-molecule inhibitors of these proteins. Teaser: MIF and D-DT exert a broad range of functions, and their expression is often dysregulated in immune-inflammatory and chronic disorders. Pharmacological strategies targeting MIF and/or D-DT could represent a novel therapeutic avenue for human diseases.