Macrophage Migration Inhibitory Factor (MIF) and Its Homologue d-Dopachrome Tautomerase (DDT) Inversely Correlate with Inflammation in Discoid Lupus Erythematosus

Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly...

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Published in:	Molecules (Basel, Switzerland) Switzerland), 2021-01, Vol.26 (1), p.184
Main Authors:	Caltabiano, Rosario, De Pasquale, Rocco, Piombino, Eliana, Campo, Giorgia, Nicoletti, Ferdinando, Cavalli, Eugenio, Mangano, Katia, Fagone, Paolo
Format:	Article
Language:	eng
Subjects:	Adult Aged Atrophy Autoimmune diseases Biological properties Biomarkers - metabolism Biopsy Chemokines Chronic conditions Correlation Cytokines d-dopachrome tautomerase Datasets Diabetes mellitus (insulin dependent) Discoid lupus erythematosus Disease Dopachrome isomerase Epidermis Epidermis - metabolism Epidermis - pathology Etiology Female Genomes Glands Guillain-Barre syndrome Homeostasis Homology Humans Immunohistochemistry Inflammation Inflammation - metabolism Inflammation - pathology Intramolecular Oxidoreductases - metabolism Kinases Lesions Lupus Lupus Erythematosus, Discoid - metabolism Lupus Erythematosus, Discoid - pathology Macrophage migration inhibitory factor Macrophage Migration-Inhibitory Factors - metabolism Male Melanoma Middle Aged Multiple sclerosis Pathogenesis Patients Plaques Proteins Scars Skin diseases
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Summary:	Discoid Lupus Erythematosus (DLE) is a chronic cutaneous disease of unknown etiology and of immunoinflammatory origin that is characterized by inflammatory plaques and may lead to disfiguring scarring and skin atrophy. Current treatments are limited, with a large proportion of patients either poorly or not responsive, which makes DLE an unmet medical need. Macrophage migration inhibitory factor (MIF) is the prototype of a pleiotropic family of cytokine that also includes the recently discovered homologue D-dopachrome tautomerase (DDT) or MIF2. MIF and DDT/MIF-2 exert several biological properties, primarily, but not exclusively of a proinflammatory nature. MIF and DDT have been suggested to play a key role in the pathogenesis of several autoimmune diseases, such as multiple sclerosis and type 1 diabetes, as well as in the development and progression of certain forms of cancers. In the present study, we have performed an immunohistochemistry analysis for the evaluation of MIF in DLE lesions and normal skin. We found high levels of MIF in the basal layer of the epidermis as well as in the cutaneous appendage (eccrine glands and sebocytes) of normal skin. In DLE lesions, we observed a significant negative correlation between the expression of MIF and the severity of inflammation. In addition, we performed an analysis of MIF and DDT expression levels in the skin of DLE patients in a publicly available microarray dataset. Interestingly, while these in silico data only evidenced a trend toward reduced levels of MIF, they demonstrated a significant pattern of expression and correlation of DDT with inflammatory infiltrates in DLE skins. Overall, our data support a protective role for endogenous MIF and possibly DDT in the regulation of homeostasis and inflammation in the skin and open up novel avenues for the treatment of DLE.
ISSN:	1420-3049 1420-3049