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Publication : Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity.

First Author  Yamanouchi J Year  2007
Journal  Nat Genet Volume  39
Issue  3 Pages  329-37
PubMed ID  17277778 Mgi Jnum  J:120349
Mgi Id  MGI:3706301 Doi  10.1038/ng1958
Citation  Yamanouchi J, et al. (2007) Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet 39(3):329-37
abstractText  Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4(+) CD25(+) regulatory T cells, which are critical for maintaining immune homeostasis.
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