Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-03

AUTHORS

Jun Yamanouchi, Dan Rainbow, Pau Serra, Sarah Howlett, Kara Hunter, Valerie E S Garner, Andrea Gonzalez-Munoz, Jan Clark, Riitta Veijola, Rose Cubbon, Show-Ling Chen, Raymond Rosa, Anne Marie Cumiskey, David V Serreze, Simon Gregory, Jane Rogers, Paul A Lyons, Barry Healy, Luc J Smink, John A Todd, Laurence B Peterson, Linda S Wicker, Pere Santamaria

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. More... »

PAGES

329-337

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1958

DOI

http://dx.doi.org/10.1038/ng1958

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052214768

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17277778


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