Transcriptomics

Dataset Information

7

Retinoic Acid Enhances Foxp3 Induction Indirectly by Relieving Inhibition from CD4(+)CD44(hi) Cells.


ABSTRACT: CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA. All gene expression profiles were obtained from highly purified T cell populations sorted by flow cytometry. To reduce variability, cells from multiple mice were pooled for sorting, and replicates were generated for essentially all groups. RNA from 0.5-3 x 105 cells was amplified, labeled, and hybridized to Affymetrix M430v2 microarrays. Raw data were preprocessed with the RMA algorithm in GenePattern, and averaged expression values were used for analysis.

ORGANISM(S): Mus musculus  

SUBMITTER: Daine Mathis   Yasmine Belkaid  CBDM Lab  Norbert Ghyselinck  Jonathan A Hill  Jason A Hall  Christophe Benoist  Cheng-Ming Sun  Qi Cai  Pierre Chambon 

PROVIDER: E-GEOD-13306 | ArrayExpress | 2008-11-16

SECONDARY ACCESSION(S): GSE13306PRJNA109885

REPOSITORIES: GEO, ArrayExpress

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Publications

Retinoic acid enhances Foxp3 induction indirectly by relieving inhibition from CD4+CD44hi Cells.

Hill Jonathan A JA   Hall Jason A JA   Sun Cheng-Ming CM   Cai Qi Q   Ghyselinck Norbert N   Chambon Pierre P   Belkaid Yasmine Y   Mathis Diane D   Benoist Christophe C  

Immunity 20081101 5


CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4  ...[more]

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