Abstract
The immunomodulator Macrophage Migration Inhibitory Factor (MIF) exerts pleiotropic immunomodulatory activities and has been implicated in the pathogenesis of diverse inflammatory diseases. Expression levels of MIF are also significantly elevated in the skin and serum of psoriasis patients, but the pathogenic significance of MIF in psoriasis is unknown. We have therefore addressed the role of MIF in two mouse models of psoriasis, namely in the imiquimod-induced psoriasiform dermatitis (IIPD) and the IL-23-induced dermatitis model. Daily treatment with Aldara™ cream, containing imiquimod, markedly increased the abundance of MIF in the skin and generated a cellular skin expression pattern of MIF closely resembling that in human plaque psoriasis. Deficiency in MIF significantly alleviated IIPD. On the clinical level, all hallmarks of psoriasiform dermatitis, including erythema, skin infiltration, and desquamation were reduced in Mif−/− mice. On the histopathological level, MIF deficiency decreased keratinocyte hyperproliferation, inflammatory cell infiltration, specifically with respect to monocyte-derived cells, and dermal angiogenesis, suggesting that MIF may be involved in the pathogenesis of psoriasiform dermatitis through several mechanisms. Similarly, MIF deficiency also significantly reduced disease in the IL-23-induced dermatitis model, suggesting that MIF is involved in the pathogenic pathways activated by IL-23 and required to achieve full-blown psoriasiform dermatitis. Collectively, our results lend support to a possible disease-promoting role of MIF in psoriasis, which should be further investigated.
Highlights
The immunomodulator Macrophage Migration Inhibitory Factor (MIF) is the earliest described lymphokine [1, 2]
The severity of psoriasiform dermatitis was significantly attenuated in Mif−/− mice compared to wild-type mice
These differences in the single clinical assessment criteria of psoriasiform dermatitis resulted in a significant decrease of the cumulative disease score by ∼40% in Mif −/− mice compared to wild-type mice at the end of the experiment on day 6 (Figures 1D,E)
Summary
The immunomodulator Macrophage Migration Inhibitory Factor (MIF) is the earliest described lymphokine [1, 2]. It is unique in its structure and biological activities, blending the properties of a cytokine, chemokine, and growth factor [3, 4]. MIF is a ligand of cell surface receptor complexes consisting of CD74 and CD44, CXCR2, CXCR4, or CXCR7 [9] It exerts pleiotropic, predominantly proinflammatory actions, such as T cell and macrophage activation, as well as chemoattraction of monocytes, neutrophils, and T cells [3, 10, 11] Predominantly proinflammatory actions, such as T cell and macrophage activation, as well as chemoattraction of monocytes, neutrophils, and T cells [3, 10, 11].
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