Il-21 and Il-21-Producing T Cells Are Involved in Multiple Sclerosis Severity and Progression Publisher Pubmed



Gharibi T^{1, 2, 3, 5} ; Hosseini A^{1, 2, 3, 5} ; Marofi F^{3, 5} ; Oraei M⁴ ; Jahandideh S^{5, 6} ; Abdollahpouralitappeh M⁷ ; Hashemi V^{5, 8} ; Motallebnezhad M⁹ ; Babaloo Z^{1, 3, 5} ; Baradaran B^{1, 3, 5} Show Affiliations
Source: Immunology Letters Published:2019

Abstract

Multiple sclerosis is a common neuroinflammatory disease of the central nervous system causing nervous system defects and severe physical disability. IL-21 is a proinflammatory cytokine produced mainly by Th-17 and Tfh cells which its exact role in MS was not yet clearly understood. In the present study we aimed to investigate the possible correlation of IL-21 gene expression, methylation, and its serum levels with MS severity and progression. The results showed that IL-21 mRNA level and serum level were significantly increased in patient group compared with control group (p = 0.02 and p < 0.0001 respectively). Moreover, we found a strong positive correlation between IL-21 mRNA levels and EDSS scores (r = 0.637, P < 0.0001), IL-21 mRNA levels and Progression Index (r = 0.540, P < 0.0001), IL-21 serum levels and EDSS scores (r = 0.617, P < 0.0001), and IL-21 serum levels and Progression Index (r = 0.527, P < 0.0001) in MS patients. Additionally, we found that the methylation level of IL-21 promoter region was decreased in patient group compared with the control group (p < 0.0001). We also found that methylation level of IL-21 gene promoter is negatively correlated with the IL-21 mRNA level (r = −0.263, p = 0.02), serum level (r = −0.249, p = 0.03), EDSS scores (r = −0.276, p = 0.01) and Progression Index (r = −0.430, p = 0.0001). Data showed that the increased percentages of IL-21-producing Tfh-like, Th-17 and Th1 cells in patients are positively correlated with MS severity and progression. The results of our study suggest a pro-inflammatory and booster role for IL-21 in the MS pathogenesis and progression. © 2019 European Federation of Immunological Societies