Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity.
Document Type
Article
Publication Date
2007
Keywords
Animals, Autoimmunity, CD4-Positive-T-Lymphocytes, CD8-Positive-T-Lymphocytes, Diabetes-Mellitus-Type-1, Homeostasis, Interleukin-2, Mice-Congenic, Mice-Inbred-NOD, T-Lymphocytes-Regulatory, Transcription-Genetic
First Page
329
Last Page
337
JAX Source
Nat Genet 2007 Mar; 39(3):329-37.
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.
Recommended Citation
Yamanouchi J,
Rainbow D,
Serra P,
Howlett S,
Hunter K,
Garner VE,
Gonzalez MA,
Clark J,
Veijola R,
Cubbon R,
Chen SL,
Rosa R,
Cumiskey AM,
Serreze DV,
Gregory S,
et a,
Santamaria P.
Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet 2007 Mar; 39(3):329-37.