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The inhibitory cytokine IL-35 contributes to regulatory T-cell function

In a recent study by the St Jude Children's Research Hospital in Memphis (USA) IL-35 could be identified as a new inhibitory , required for maximal suppressive activity.

IL-35 is probably produced specifically by Treg cells, a sub-population of 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 -induced gene 3 (, encodes beta) and α (Il12a, encodes α/p35) are highly expressed by murine + (forkhead box P3) Treg cells but not by resting or activated effector . Also, an -α heterodimer is secreted by Treg.

as well as Il12a mRNA are upregulated in Treg cells that are kept in co-culture with effector CD4+ T cells, thereby boosting and α production. is a downstream target of , a transcription factor necessary for the development and function of Treg cells. Experiments showed that -/- 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 family members, which is why this new -α heterodimer has been named interleukin-35 (IL-35). Ectopic expressed IL-35 transfers regulatory activity on naive and recombinant IL-35 suppresses proliferation of .

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