Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity.
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
Nat Genet 2007 Mar; 39(3):329-37.
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.
Yamanouchi, J; Rainbow, D; Serra, P; Howlett, S; Hunter, K; Garner, V E.; Gonzalez, Munoz A.; Clark, J; Veijola, R; Cubbon, R; Chen, S L.; Rosa, R; Cumiskey, A M.; Serreze, D V.; Gregory, S; et, al; and Santamaria, P, "Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity." (2007). Faculty Research 2000 - 2009. 1538.