期刊
INTERNATIONAL IMMUNOLOGY
卷 20, 期 2, 页码 223-234出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxm139
关键词
IL-27; STAT1; STAT3; TGF beta; treg
类别
资金
- Austrian Science Fund (FWF) [F 2803] Funding Source: researchfish
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 beta (TGF beta)-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 TGF beta-induced Treg cells, the cells generated after differentiation in the presence of TGF beta and IL-27 maintained the ability for IL-2 and tumour necrosis factor alpha (TNF alpha) 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, TGF beta blocked IL-27-induced T(h)1 differentiation. Thus, IL-27 and TGF beta mutually control their effects on CD4+ T-cell differentiation, whereby IL-27 favours inflammatory conditions through a STAT3-dependent inhibition of Treg generation.
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