Functional MIF promoter haplotypes modulate Th17-related cytokine expression in peripheral blood mononuclear cells from control subjects and rheumatoid arthritis patients

• Published in: Cytokine (Philadelphia, Pa.) Vol. 115; pp. 89 - 96
• Main Authors: Hernández-Palma, Luis Alexis, García-Arellano, Samuel, Bucala, Richard, Llamas-Covarrubias, Mara Anaís, De la Cruz-Mosso, Ulises, Oregon-Romero, Edith, Cerpa-Cruz, Sergio, Parra-Rojas, Isela, Plascencia-Hernández, Arturo, Muñoz-Valle, José Francisco
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.03.2019
• Subjects: Adult; Arthritis, Rheumatoid - genetics; Cytokines - genetics; Female; Haplotypes; Haplotypes - genetics; Humans; Intramolecular Oxidoreductases - genetics; Leukocytes, Mononuclear - metabolism; Lipopolysaccharide; Macrophage Migration-Inhibitory Factors - genetics; Male; Middle Aged; MIF; Polymorphism, Genetic - genetics; Promoter Regions, Genetic - genetics; Rheumatoid arthritis; Th17 Cells - metabolism; Th17 profile cytokines; Haplotypes; Lipopolysaccharide; MIF; Th17 profile cytokines; Rheumatoid arthritis
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2018.11.014

•MIF and LPS induce the Th17 cytokine secretion profile in PBMC from RA patients.•In a Mexican-Mestizo population, the most frequent MIF haplotypes were 5G, 6G, and 7C.•MIF haplotypes modulate the secretion of cytokines related to the Th17 profile in PBMC cultures. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by elevated levels of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-17, and macrophage migration inhibitory factor (MIF). MIF induces IL-17 secretion and MIF promoter polymorphisms influence the expression of selected downstream mediators. The aim of this study was to investigate the relationship between known functional MIF haplotypes and Th17-related cytokine secretion profile in peripheral blood mononuclear cells (PBMC) from control subjects (CS) and RA patients stimulated with lipopolysaccharide (LPS) and recombinant human MIF (rhMIF). The −794 CATT5-8 and −173G > C polymorphisms of the MIF gene were determined by conventional PCR and PCR-RFLP, respectively. The most frequent haplotypes of the MIF polymorphism and PBMC were identified from three subjects homozygous for each haplotype and in both study groups, the PBMC were obtained and stimulated with LPS or rhMIF. The secretion of cytokines related to the Th17 profile was determined by a multiplex immunoassay (MAGPIX). LPS stimulation induced the secretion of cytokines related to the Th17 profile in PBMC from CS and RA patients, whereas, rhMIF only stimulated this response in PBMC from RA patients. PBMC from CS carriers of the MIF 7C haplotype showed more IL-17A, IL-17F, IL-22, and IL-23 secretion than non-7C carriers after LPS stimulation. In the case of rhMIF stimulation, the PBMC from CS carriers of the 7C haplotype secreted more IL-17A and IL-23 than non-7C carriers. In conclusion, genetic variants of the MIF promoter modulate the secretion of cytokines related to the Th17 profile in PBMC from CS inducing a differential response in comparison to PBMC from RA patients.