Upregulated Expression of Macrophage Migration Inhibitory Factor, Its Analogue D-Dopachrome Tautomerase, and the CD44 Receptor in Peripheral CD4 T Cells from Clinically Isolated Syndrome Patients with Rapid Conversion to Clinical Defined Multiple Sclerosis

Abstract

Background and objectives: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. Materials and Methods: We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Results: Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4+ T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4+ T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4+ T cells, as other immune cells including CD8+ T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Conclusions: Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4+ T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

“…We also studied the possible diagnostic and prognostic value of TSPAN32 expression in PBMC of MS patients, on the course of the disease. The use of whole-genome expression databases has been largely exploited [25][26][27][28] for the characterization of pathogenic pathways and to identify therapeutic targets for a variety of disorders, including immunoinflammatory and autoimmune diseases [29][30][31][32][33][34][35][36], cancer [37][38][39], and has allowed dismantling pathogenetic pathways [40][41][42], along with the identification of novel tailored therapeutic targets [43][44][45][46].…”

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

“…MIF, and more recently DDT, have been implicated in the pathogenesis of several pathologies, including immunoinflammatory and autoimmune diseases (38,(42)(43)(44) and cancer (45)(46)(47). As anticipated above, that MIF may represent an important pathogenic molecule in the pathogenesis of AUD emerges from recent studies indicating that the dual inhibitor of phosphodiesterase-4 and -10 and MIF, named IBUD, has beneficial effects of AUD both in rodent models and human patients (31,32).…”

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

“…In the present study, we first analyzed the expression levels of IL37, SIGIRR, and IL18R1 in circulating immune cells from MS patients. In particular, we performed a DNA microarray analysis that represents a useful in silico tool for the better understanding of pathogenic pathways and the possible prediction of novel diagnostic therapeutic strategies, as it has been shown in a variety of clinical settings, such as autoimmune and immunoinflammatory diseases [38][39][40][41][42][43][44] and cancer [45][46][47][48][49][50][51], leading to the identification of novel therapeutic targets [52][53][54][55].…”