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E-GEOD-63455 - IL-27 stimulation in Foxp3+ Tregs improves suppressive function and therapeutic efficacy

Status
Released on 1 November 2015, last updated on 3 December 2015
Organism
Mus musculus
Samples (8)
Array (1)
Protocols (7)
Description
Foxp3 expressing regulatory T cells (Tregs) are the central regulator of immune homeostasis and tolerance. As it is believed that proper Treg function is compromised under inflammatory conditions, exploring a pathway that enhances Treg function is of great importance. In this study, we report that IL-27, an IL-12 family cytokine known to play both pro- and anti-inflammatory role in T cells, plays a pivotal role in Treg function to control T cell-induced colitis. Unlike WT Tregs capable of inhibiting colitogenic T cell expansion and inflammatory cytokine expression, IL-27R-deficient Tregs were unable to downregulate inflammatory T cell responses. Tregs stimulated with IL-27 expressed substantially enhanced suppressive function both in vitro and in vivo. IL-27 stimulation of Tregs induced expression of LAG3, a surface molecule implicated in negatively regulating immune responses. LAG3 expression in IL-27-stimulated Tregs was critical to mediate suppressive Treg function. Finally, human Tregs also displayed enhanced suppressive function and LAG3 expression in response to IL-27 stimulation. Taken together, our results highlight a novel function of the IL-27/LAG3 axis in Treg regulation of inflammatory responses in the intestine. FACS purified Foxp3+ Tregs were stimulated in the presence of media or IL-27 to compare IL-27 induced gene profiles. Four samples (media stimulated or IL-27-stimulated) were collected from four independent experiments. Genes altered by IL-27 treatment were compared to those of media stimulated Tregs.
Experiment type
transcription profiling by array 
Contacts
Yibayiri Osee Sanogo <geo@ncbi.nlm.nih.gov>, Booki Min, Jeongsu Do, Yibayiri O Sanogo
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-63455.idf.txt
Sample and data relationshipE-GEOD-63455.sdrf.txt
Processed data (1)E-GEOD-63455.processed.1.zip
Additional data (1)E-GEOD-63455.additional.1.zip
Array designA-GEOD-19441.adf.txt
Links