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Nat Genet. 2007 Mar;39(3):329-37. Epub 2007 Feb 4.

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

Author information

1
Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology and Infectious Diseases, Institute of Inflammation, Infection and Immunity, Faculty of Medicine, The University of Calgary, Calgary, Alberta T2N 4N1, Canada.

Abstract

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.

PMID:
17277778
PMCID:
PMC2886969
DOI:
10.1038/ng1958
[Indexed for MEDLINE]
Free PMC Article

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