Macrophage Migration Inhibitory Factor (MIF) Drives Murine Psoriasiform Dermatitis

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.

Pathogenetic Therapy of Psoriasis by Muramyl Peptide

“…Elevated levels of sCD54 and MIF in the serum of patients with psoriasis and control over their dynamics have prognostic significance in determining both the severity of the disease and the effectiveness of the therapy. The obtained data are consistent with the results of other researchers, indicating the value of serum markers sCD54 (31) and MIF (32, 33) in the pathogenesis of psoriasis, and can be considered as potential biomarkers and targets for immunomodulating therapies for psoriasis. Standardized serum markers measurement is available for clinical use and analysis of secreted protein after treatment by immunomodulators would offer a prognostic factor of the therapy effectiveness.…”

MIF-Dependent Control of Tumor Immunity

“…Not coincidentally, the addition of rMIF to RA patient-derived PBMCs increases IL-17 expression to levels similar to that observed with PBMCs from an individual with a high expression MIF polymorphism haplotype (175). Finally, using a murine model of psoriasiform dermatitis induced by IL-23-a critical determinant of Th17 lymphocyte responses (178)-MIFdeficiency resulted in a dramatic reduction of disease progression (179).…”

<p>Assessment of macrophage migration inhibitory factor in patients with verruca vulgaris</p>

“…Clues for the role of MIF in wart progression come from the observation that it has been investigated in many clinical and experimental studies in both inflammatory diseases and cancer20 specifically its role is in stimulating proliferation of keratinocytes in psoriasis animal models 21…”