Thus, our study identifies miR-146a as an important molecular brake that blocks the autocrine IL-6- and IL-21-induced Th17 differentiation pathways in autoreactive CD4 T cells, highlighting its potential as a therapeutic target for treating autoimmune diseases.
Although the early studies on IL-17 focused on Th17 cells, it was later demonstrated that γδ T cells were an important early source of IL-17 and IL-21 that helped amplify IL-17 production by Th17 cells in autoimmune diseases.
Accordingly, SFN significantly inhibited the activation of untransformed human T-cells derived from healthy donors or RA patients, and downregulated the expression of the transcription factor RORγt, and the T<sub>H</sub>17-related cytokines IL-17A, IL-17F, and IL-22, which play a major role within the pathophysiology of many chronic inflammatory/autoimmune diseases.
This study therefore elucidates critical mechanism for IL-21-induced Th17 differentiation to indicate SKI and SMAD4 as potential therapeutic targets for treating autoimmune diseases.
Plasma cytokine analysis confirms elevation of multiple autoimmunity-related cytokines (e.g., TNF-α, IL17A-D, IL-22) in people with DS, independent of diagnosis of autoimmunity.