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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 1.022 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i6.50
pages 559-570

IL-21 Is an Immune Activator That also Mediates Suppression via IL-10

Rosanne Spolski
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD
Warren J. Leonard
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, Bethesda, MD

ABSTRACT

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.


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