3.2. IL-21/ IL-23
Besides IL-6 and TGF-β, the cytokines IL-21 and IL-23 also signal via STAT3 and are critical for the differentiation of both murine and human Th17 cells. IL-21, a member of the IL-2 cytokine family, is mainly secreted by CD4+ T, natural killer (NK), and Th17 cells[31]. Both in vivo and in vitro, it was confirmed that mice with IL-21 receptor loss had a reduced Th17 cell response in the presence of IL-6. These findings suggest that IL-21 is produced by newly differentiated Th17 cells that promote differentiation into autosecretory Th17 cells[32]. IL-21 is mainly produced by Th17 cells. It is induced by IL-6 during Th17 cell differentiation and may function in an autocrine manner to maintain the Th17 polarising signal. IL-23 in particular is required for the function of pathogenic Th17 cells and their ability to cause autoimmunity[33]. IL-23 promotes the secretion of IL-17 to produce inflammatory response, which has been demonstrated to increase IL-17 production by stabilising IL-17 expression, although this cytokine alone is not sufficient to induce Th17 differentiation. IL-1β, together with IL-6, plays an important role in the expansion of Th17 cells and the maintenance of IL-23 production in the Th17 cell population. In human cells, the binding of TGF-β and IL-21 is sufficient to induce naive CD4 + T cells to differentiate into Th17 cells.