IL-27 controls the development of inducible regulatory T cells and Th17 cells via differential effects on STAT1.
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.
Neufert
Clemens
C
Laboratory of Immunology, I Medical Clinic, University of Mainz, Mainz, Germany.
Becker
Christoph
C
Wirtz
Stefan
S
Fantini
Massimo C
MC
Weigmann
Benno
B
Galle
Peter R
PR
Neurath
Markus F
MF
D000818:Animals; D018920:Coculture Techniques; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D050794:STAT1 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C486767:Il27 protein, mouse; D007378:Interleukins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse