IL21 is a type I four-α-helix bundle cytokine that belongs to the IL2 family and functions as a "growth hormone"like cytokine. After the antigen-responsive differentiation phase, Th17 cells enter the amplification stage, and IL21 plays a pivotal role in the expansion and differentiation of the Th17 lineage, providing an autocrine and paracrine stimulus for Th17 cells [41, 87] . During clonal expansion, IL21 also promotes IL23R expression in differentiated Th17 cells, which plays an important role in the stabilization of the Th17 lineage in the presence of IL23 [88] . Although no effects were observed when Il21 was administered after EAE progression, the administration of IL21 boosted natural killer (NK) cell functions before the induction of EAE, including the secretion of Ifnγ. Therefore, IL21, by affecting NK cells, has various effects during the initiation and progression of EAE [89] .