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Advances in Understanding the Role of MIF in the Pathogenesis of Autoimmune Diseases

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MIF Family Cytokines in Innate Immunity and Homeostasis

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Macrophage migration inhibitory factor (MIF) is an immunoregulatory cytokine that was first noted several decades ago for its property to arrest the random movement of macrophages. It is now known that MIF has pluripotent effects including promoting the expression of proinflammatory cytokines, having chemokine-like functions, and promoting cell migration and recruitment. Moreover, it plays an important role in sustaining immune cell survival by inhibiting activation-induced apoptosis. The cell surface receptor for MIF has been identified as the CD74 molecule, and functional interactions with the CXCR2/4 chemokine receptors also occur. CD74 is present on multiple cell types; thus, the function of MIF is defined by the cell type on which it acts. MIF is a critical upstream regulator of both innate and adaptive immune responses. Because of its broad range of activities, MIF has been implicated in the pathogenesis of a variety of infectious, inflammatory, and autoimmune disease conditions including rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. During autoimmune diseases, the overproduction of MIF may potentiate inflammation and priming of autoreactive cells and enhance detrimental effects on affected tissues. In addition, MIF has a unique relationship with corticosteroids (CSs); it can override the effects of CSs and may be important in corticosteroid resistance. In vitro and in vivo evidence has focused attention on MIF as a new therapeutic target for autoimmune diseases by selectively neutralizing MIF with antibodies or specific small molecule inhibitors.

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Authors and Affiliations

  1. Department of Biology, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX, 78249, USA

    Saisha A. Nalawade & Thomas G. Forsthuber

  2. Centers for Biomedical Science, Feinstein Institute for Medical Research, Manhasset, NY, 11030, USA

    Yousef Al-Abed

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  1. Saisha A. Nalawade
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  2. Yousef Al-Abed
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  3. Thomas G. Forsthuber
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Correspondence to Thomas G. Forsthuber .

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  1. The Anlyan Center, Yale School of Medicine, Yale University, New Haven, Connecticut, USA

    Richard Bucala

  2. Department of Vascular Biology, Institute for Stroke and Dementia Research, Ludwig-Maximilians-University (LMU), Munich, Germany

    Jürgen Bernhagen

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Nalawade, S.A., Al-Abed, Y., Forsthuber, T.G. (2017). Advances in Understanding the Role of MIF in the Pathogenesis of Autoimmune Diseases. In: Bucala, R., Bernhagen, J. (eds) MIF Family Cytokines in Innate Immunity and Homeostasis. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-52354-5_5

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