%0 Journal Article %A Spolski , Rosanne %A Leonard, Warren J. %D 2010 %I Begell House %K IL-21, IL-10, autoimmunity, Tr1 cell, EAE, SLE %N 6 %P 559-570 %R 10.1615/CritRevImmunol.v30.i6.50 %T IL-21 Is an Immune Activator That also Mediates Suppression via IL-10 %U https://www.dl.begellhouse.com/journals/2ff21abf44b19838,7bdc9a133b3ff311,3cf2e98a7cd9711b.html %V 30 %X Interleukin-21 (IL-21) is a pleiotropic type I cytokine that is produced predominantly by CD4+ T cells and natural killer T (NKT) cells. Although IL-21 production is relatively restricted to these two populations of immune cells, its targets are numerous, including multiple lympho-hematopoietic as well as non-hematopoietic lineages. The effects of IL-21 are specific not only to the target cell type, but also depend on the developmental stage of the target cell as well as the available co-stimulatory signals. Accordingly, IL-21 functions not only as a strong inducer of differentiation and proliferation but also as a pro-apoptotic factor. Although most of the effects of IL-21 are immunostimulatory, it has become clear that one of the cytokines that is potently induced by IL-21 in a number of lymphoid lineages is interleukin-10 (IL-10), one of the most immunosuppressive cytokines. The seemingly contradictory actions of IL-21 and IL-10 and the consequences of their co-expression are currently being explored in numerous infectious models, autoimmune diseases, and tumor responses. This review seeks to critically evaluate the evidence concerning the regulation of IL-10 by IL-21 in a number of lineage subsets as well as to discuss the potential positive versus deleterious roles that this co-expression may play in a range of disease models. %8 2010-12-09