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The inhibitory cytokine IL-35 contributes to regulatory T-cell function
Areas: Cytokines, Immunology
In a recent study by the St Jude Children's Research Hospital in Memphis (USA) IL-35 could be identified as a new inhibitory cytokine, required for maximal suppressive activity.
IL-35 is probably produced specifically by Treg cells, a sub-population of CD4+ T-cells essential for upholding self-tolerance and preventing autoimmunity. Treg cells also limit chronic inflammatory diseases like asthma and inflammatory bowel disease and regulate homeostatic lymphocyte expansion. On the other hand they suppress the natural immune response to parasites and viruses but also to therapeutic anti-tumour vaccines.
The Epstein-Barr-virus-induced gene 3 (Ebi3, encodes IL-27beta) and interleukin-12 α (Il12a, encodes IL-12α/p35) are highly expressed by murine Foxp3+ (forkhead box P3) Treg cells but not by resting or activated effector CD4+ T-cells. Also, an Ebi3-IL-12α heterodimer is secreted by Treg.
Ebi3 as well as Il12a mRNA are upregulated in Treg cells that are kept in co-culture with effector CD4+ T cells, thereby boosting Ebi3 and IL-12α production. Ebi3 is a downstream target of Foxp3, a transcription factor necessary for the development and function of Treg cells. Experiments showed that Ebi3 -/- and Il12a -/- Treg cells regulary activity is reduced in vitro and they are unable to control homeostatic proliferation or to heal inflammatory bowel disease in vivo.
These characteristics in phenotype are different from other IL-12 family members, which is why this new Ebi3-IL-12α heterodimer has been named interleukin-35 (IL-35). Ectopic expressed IL-35 transfers regulatory activity on naive T-cells and recombinant IL-35 suppresses proliferation of T-cells.
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26.03.2008 | Anna Lena Marwedel 
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