Targeting Interleukin-21 in Immune-Mediated Pathologies
Massimiliano Sarra, Francesco Pallone, Thomas T. Macdonald and Giovanni Monteleone
Affiliation: Dipartimento di Medicina Interna, Universita Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy.
Interleukin (IL)-21, a cytokine mostly produced by activated CD4+ T cells, has been reported to play an important role in the tissue-damaging immune response in various organs. This pathogenic effect is strictly linked to the ability of IL-21 to control the functional activities of multiple immune and non-immune cells. For instance, IL-21 regulates the differentiation and function of effector CD4+ T helper cells, controls activation, proliferation, and survival of B cells and enhances the cytotoxic activity of CD8+ T cells and NK cells. IL-21 also inhibits the differentiation of inducible regulatory T cells (Tregs), while making effector CD4+ T cells resistant to the Tregs-mediated immunosuppression. Additionally, IL-21 stimulates epithelial cells and fibroblasts to make chemokines and extracellular matrix proteases, respectively. Consistently, studies from various laboratories have documented the beneficial effect of IL-21 neutralization on the progression of inflammatory diseases in mice. Here we review the present knowledge on the expression and role of IL-21 in immune-mediated pathologies.
Keywords: IL-21, IBD, diabetes, rheumatoid arthritis, atopic dermatitis, lupus
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