IL-21 receptor expression determines the temporal phases of experimental autoimmune encephalomyelitis

The IL-21 receptor (IL-21R) consists of a unique subunit and a common gamma chain (gamma(c)) that is shared with other cytokines including IL-2, IL-4, IL-7, and IL-15. The interaction between IL-21 and IL-21R results in significant effects on both innate and adaptive immune responses. In this study we examined the influence of IL-21R deficiency (IL-21R(-/-)) on the development of experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis (MS). IL-21R(-/-) mice developed EAE earlier and more severe neurological impairment than control mice, yet those mice could effectively recover from neurological deficits. The impact on EAE initiation by IL-21R deficiency was associated with a defect of CD4(+)CD25(+) T regulatory (Treg) cells and a down-regulated expression of Foxp3. The recovery from IL-21R(-/-) EAE was correlated with an expansion of Treg cells as well as an organ-specific redistribution of NK cells. These results suggest that a temporal influence of IL-21 on the activity of immunoregulatory circuits can be important in the modulation of the course of the autoimmune disease.