MIF functional polymorphisms (-794 CATT5-8 and -173 G&gt;C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population

Castañeda-Moreno, V.A.; Cruz-Mosso, Ulises De la; Torres-Carrillo, Norma; Macías-Islas, Miguel Ángel; Torre, Ofelia Padilla-De la; Mireles-Ramírez, Mario Alberto; González-Pérez, Óscar; Ruiz-Sandoval, José Luís; Huerta, Miguel; Trujillo, Xóchitl; Ortuño-Sahagún, Daniel; Muñoz‐Valle, José Francisco

doi:10.1016/j.jneuroim.2018.04.006

Cited by 20 publications

(22 citation statements)

References 40 publications

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“…Macrophage migration inhibitory factor (MIF) and its receptors are expressed in elevated levels by different cell types in SLE (5), and circulating MIF level correlates with disease activity (6). High expression MIF alleles also are linked to disease severity in different populations (7, 8). MIF binds to a receptor complex comprising CD74 and CD44 to activate the phosphorylation of ERK and AKT, leading to the expression of pro-inflammatory cytokines such as IL-1β, IL-6, IL-8, TNF-α, and others (9–11).…”

Section: Introductionmentioning

confidence: 99%

MiRNA Regulation of MIF in SLE and Attenuation of Murine Lupus Nephritis With miR-654

Guo

et al. 2019

Front. Immunol.

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Objective: Macrophage Migration Inhibitory Factor (MIF) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis (LN). MicroRNAs (miRNAs) play important roles in LN but whether specific miRNAs regulate the expression of MIF in LN is unknown. We explore specific miRNAs that can regulate MIF expression, and investigate miR-654 for the treatment of experimentally-induced murine lupus nephritis.Methods: Sera samples from 24 SLE patients and 24 controls were collected to measure the MIF concentration and its correlation with disease activity. A luciferase reporter assay was used to explore the target of miR-654. ELISA was used to detect the downstream cytokines regulated by miR-654 and MIF. Western blot was applied to measure the impact of miR-654 inhibition on downstream MIF signaling. The therapeutic efficacy of miR-654 was tested in the pristine-induced lupus mouse model. We further measured miR-654 expression and analyzed its relationship with MIF expression in SLE patients.Results: The serum MIF level was increased in SLE patients (p < 0.001) and positively correlated with the SLEDAI score (r = 0.5473; p = 0.0056). MiR-654 inhibited MIF and downstream inflammatory cytokine production by selectively inhibiting the phosphorylation of ERK and AKT. Activation of miR-654 reduced IL-1β, IL-6, IL-8, and TNF-α production, reduced gomerulonephritis, and decreased MIF, IgG, and C3 expression in murine lupus glomeruli. Furthermore, MIF was negatively correlated with miR-654 expression (r = −0.4644; p = 0.0222) in SLE patients.Conclusion: MiR-654 negatively correlated with MIF and disease activity in patients with SLE. MiR-654 inhibits MIF expression via binding to MIF 3'UTR, selectively suppresses the phosphorylation of ERK and AKT, and reduces downstream inflammatory cytokine production. In vivo miR-654 treatment decreases MIF and downstream cytokine production and ameliorates murine lupus nephritis.

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Section: Introductionmentioning

confidence: 99%

MiRNA Regulation of MIF in SLE and Attenuation of Murine Lupus Nephritis With miR-654

Guo

et al. 2019

Front. Immunol.

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“…Automated capillary electrophoresis on a DNA sequencer was performed on each sample and the -794 CATT5-8 repeat length was identified using Genotyper 3.2 software (Applied Biosystems). Although at least eight additional polymorphisms have been identified within the human MIF locus, these additional variants (all SNPs) are rare and have a low likelihood of functionality given their location in introns or within the 3 0 UTR [47].…”

Section: Mif -794 Catt5-8 Genotypingmentioning

confidence: 99%

“…Increased MIF promoter activity is proportional to increased numbers of the CATT repeats at position -794. Furthermore, the CATT7 allele is strong linkage disequilibrium with the -173 C allele [26,35,36,47,48].…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor in Nodding syndrome

et al. 2021

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Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)–a parasitic worm transmitted to human by blackflies. NS seems to be an ’Autoimmune Epilepsy’ in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a −794 CATT5–8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF -173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS.Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expression MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy.

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“…Recent work from our laboratory and others has shown that MDSCs are increased in the circulation and tumor microenvironment (12), they portend a poor prognosis (8), their expansion can be driven by CSCderived MIF (8,13), and they can be reduced by MIF neutralization (either genetically or pharmacologically) (9,14). Furthermore, MIF has been studied in a variety of cancers in the context of inflammation and has been found to regulate immune activity (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32). However, MIF has not been explored in the context of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

The MIF SNP rs755622 is a germline determinant of tumor immune activation in Glioblastoma

Alban

Grabowski

Otvos

et al. 2022

Preprint

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While immunotherapies have shown durable responses for multiple tumors, their efficacy remains limited in some advanced cancers, including glioblastoma. This may be due to differences in the immune landscape, as the glioblastoma microenvironment strongly favors immunosuppressive myeloid cells, which are linked to an elevation in immune-suppressive cytokines, including macrophage migration inhibitory factor (MIF). We now find that a single-nucleotide polymorphism (SNP) rs755622 in the MIF promoter associates with increased leukocyte infiltration in glioblastoma. Furthermore, we identified lactotransferrin expression as being associated with the rs755622 SNP, which could also be used as a biomarker for immune infiltrated tumors. These findings provide the first example in glioblastoma of a germline SNP that underlies differences in the immune microenvironment and identifies high lactotransferrin as a potential factor promoting immune activation.

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MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population

Cited by 20 publications

References 40 publications

MiRNA Regulation of MIF in SLE and Attenuation of Murine Lupus Nephritis With miR-654

MiRNA Regulation of MIF in SLE and Attenuation of Murine Lupus Nephritis With miR-654

Macrophage migration inhibitory factor in Nodding syndrome

The MIF SNP rs755622 is a germline determinant of tumor immune activation in Glioblastoma

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