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

Published

Journal Article

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.

Full Text

Cited Authors

  • Yamanouchi, J; Rainbow, D; Serra, P; Howlett, S; Hunter, K; Garner, VES; Gonzalez-Munoz, A; Clark, J; Veijola, R; Cubbon, R; Chen, S-L; Rosa, R; Cumiskey, AM; Serreze, DV; Gregory, S; Rogers, J; Lyons, PA; Healy, B; Smink, LJ; Todd, JA; Peterson, LB; Wicker, LS; Santamaria, P

Published Date

  • March 2007

Published In

Volume / Issue

  • 39 / 3

Start / End Page

  • 329 - 337

PubMed ID

  • 17277778

Pubmed Central ID

  • 17277778

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng1958

Language

  • eng