6533b7defe1ef96bd1276967
RESEARCH PRODUCT
IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1
Stefan WirtzChristoph BeckerPeter R. GalleMarkus F. NeurathBenno WeigmannClemens NeufertMassimo Fantinisubject
medicine.medical_treatmentImmunologyMice Transgenicchemical and pharmacologic phenomenaInflammationBiologyT-Lymphocytes RegulatoryProinflammatory cytokineMiceImmune systemT-Lymphocyte SubsetsmedicineAnimalsImmunology and AllergySTAT1IL-2 receptorTranscription factorInterleukinsFOXP3Forkhead Transcription FactorsFlow CytometryCoculture TechniquesCell biologySTAT1 Transcription FactorCytokineImmunologybiology.proteinmedicine.symptomdescription
IL-27 is an IL-12-related cytokine frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. Here, we have analyzed the mechanisms how IL-27 may drive such divergent immune responses. While IL-27 suppressed the development of proinflammatory Th17 cells, a novel role for this cytokine in inhibiting the development of anti-inflammatory, inducible regulatory T cells (iTreg) was identified. In fact, IL-27 suppressed the development of adaptive, TGF-beta-induced Forkhead box transcription factor p3-positive (Foxp3(+)) Treg. Whereas the blockade of Th17 development was dependent on the transcription factor STAT1, the suppression of iTreg development was STAT1 independent, suggesting that IL-27 utilizes different signaling pathways to shape T cell-driven immune responses. Our data thus demonstrate that IL-27 controls the development of Th17 and iTreg cells via differential effects on STAT1.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2007-06-04 | European Journal of Immunology |