Recent work has implicated a novel Th effector cell subset, the Th17 cell subset, in the development of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) because of the ability of Th17 cells to produce cytokines like IL-17 and IL-21 that can drive both inflammatory and humoral responses.
B cell proliferation inducing cytokine IL-21 was higher expressed in LN biopsies of RA patients compared with HC and expression was not affected by rituximab treatment.
Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls.
The expression of IL-21R and IL-21 was analyzed by TaqMan real-time polymerase chain reaction (PCR) and in situ hybridization of synovial biopsy samples from patients with RA and osteoarthritis (OA).
The aim of this study was to evaluate the relationship between the cytokines IL-15, IL-21, and IFN-γ with the autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) in RA and disease activity.
Leptin-stimulated RA PBMC upregulated CD4<sup>+</sup>CXCR5<sup>+</sup>ICOS<sup>+</sup> T cells, along with increased IL-6, IL-21, and IL-12.CD4<sup>+</sup>CXCR5<sup>+</sup>ICOS<sup>+</sup> T cells, Bcl-6 mRNA expression, pSTAT1, and pSTAT3 obviously declined when anti-IL-6R antibody was added into leptin-treated RA PBMC, which suggested that leptin upregulated RA CD4<sup>+</sup>CXCR5<sup>+</sup>ICOS<sup>+</sup> T cells via increased IL-6 by activation of STAT1 and STAT3.
Higher mRNA expression of Bcl-6 and lower Blimp-1 mRNA expression were observed in patients with RA compared to healthy controls, and the expression level of IL-21 was higher in RA patients, which was also seen in CIA mice.