International Immunology Advance Access originally published online on December 21, 2007
International Immunology 2008 20(2):223-234; doi:10.1093/intimm/dxm139
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IL-27 inhibits the development of regulatory T cells via STAT3
1 Institut für Medizinische Mikrobiologie und Hygiene, Universität Marburg, Hans-Meerwein-Straße 2, 35043 Marburg, Germany
2 Department für Mikrobiologie und Immunologie, Universität Wien, Dr Bohr-Gasse 9, 1030 Wien, Austria
Correspondence to: M. Huber; E-mail: huberma{at}med.uni-marburg.de
Regulatory CD4+ T cells are important for the homeostasis of the immune system and their absence correlates with autoimmune disorders. Here, we investigate the capacity of IL-27, a cytokine with pro- and anti-inflammatory properties, to regulate the generation of transforming growth factor β (TGFβ)-inducible forkhead box P3 (Foxp3)-positive regulatory T (Treg) cells. Our results demonstrate that IL-27 inhibits the acquisition of the Treg phenotype at the level of Foxp3, CD25 and CTLA-4 (CD152) expression as well as the suppressive function. In contrast to TGFβ-induced Treg cells, the cells generated after differentiation in the presence of TGFβ and IL-27 maintained the ability for IL-2 and tumour necrosis factor 
(TNF) production. The inhibitory effect of IL-27 on Treg generation was at least partially signal transducer and activator of transcription 3 (STAT3) dependent as examined by targeted STAT3 protein inhibition using small interfering RNA (siRNA), while STAT1-dependent signals seemed to oppose the STAT3 signals. In turn, TGFβ blocked IL-27-induced Th1 differentiation. Thus, IL-27 and TGFβ mutually control their effects on CD4+ T-cell differentiation, whereby IL-27 favours inflammatory conditions through a STAT3-dependent inhibition of Treg generation.
Keywords: IL-27, STAT1, STAT3, TGFβ, Treg
Transmitting editor: A. Radbruch
Received 23 October 2007, accepted 22 November 2007.
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