As IL-6 and IL-21 are both important in inducing IL-23 receptor expression in naïve CD4+ T cells, this combined blockade might reduce IL-23R expression levels, and thereby IL-23 signaling, to a minimum, possibly contributing to the major reduction in Th17 levels [20,22], In line with previously published data, arthritis severity was significantly reduced in IL-6-/- mice as compared to WT controls, two days after arthritis induction [33]. Here, CD4 is linked to arthritic joint disease.