| First Author | Vogelzang A | Year | 2014 |
| Journal | J Immunol | Volume | 192 |
| Issue | 4 | Pages | 1404-14 |
| PubMed ID | 24446516 | Mgi Jnum | J:209356 |
| Mgi Id | MGI:5567015 | Doi | 10.4049/jimmunol.1302285 |
| Citation | Vogelzang A, et al. (2014) IL-21 contributes to fatal inflammatory disease in the absence of Foxp3+ T regulatory cells. J Immunol 192(4):1404-14 |
| abstractText | The cytokine IL-21 has been shown to influence immune responses through both costimulatory effects on effector T cells and opposing inhibitory effects on T regulatory cells (Tregs). To distinguish the effect of IL-21 on the immune system from that of its effect on Tregs, we analyzed the role of IL-21/IL-21R signaling in mice made genetically deficient in IL-2, which exhibit a deficit in IL-2-dependent Foxp3 regulatory T cells and suffer from a fatal multiorgan inflammatory disease. Our findings demonstrate that in the absence of IL-21/IL-21R signaling, Il2(-/-) mice retained a deficiency in Tregs yet exhibited a reduced and delayed inflammatory disease. The improved health of Il2(-/-)Il21r(-/-) mice was reflected in reduced pancreatitis and hemolytic anemia and this was associated with distinct changes in lymphocyte effector populations, including the reduced expansion of both T follicular helper cells and Th17 cells and a compensatory increase in IL-22 in the absence of IL-21R. IL-21/IL-21R interactions were also important for the expansion of effector and memory CD8(+) T cells, which were critical for the development of pancreatitis in Il2(-/-) mice. These findings demonstrate that IL-21 is a major target of immune system regulation. |
