• Home
  • Search Results
  • Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3.

Imbalanced signal transduction in regulatory T cells expressing the transcription factor FoxP3.

Proceedings of the National Academy of Sciences of the United States of America (2015-12-03)
Dapeng Yan, Julia Farache, Michael Mingueneau, Diane Mathis, Christophe Benoist
ABSTRACT

FoxP3(+) T regulatory (Treg) cells have a fundamental role in immunological tolerance, with transcriptional and functional phenotypes that demarcate them from conventional CD4(+) T cells (Tconv). Differences between these two lineages in the signaling downstream of T-cell receptor-triggered activation have been reported, and there are different requirements for some signaling factors. Seeking a comprehensive view, we found that Treg cells have a broadly dampened activation of several pathways and signaling nodes upon TCR-mediated activation, with low phosphorylation of CD3ζ, SLP76, Erk1/2, AKT, or S6 and lower calcium flux. In contrast, STAT phosphorylation triggered by interferons, IL2 or IL6, showed variations between Treg and Tconv in magnitude or choice of preferential STAT activation but no general Treg signaling defect. Much, but not all, of the Treg/Tconv difference in TCR-triggered responses could be attributed to lower responsiveness of antigen-experienced cells with CD44(hi) or CD62L(lo) phenotypes, which form a greater proportion of the Treg pool. Candidate regulators were tested, but the Treg/Tconv differential could not be explained by overexpression in Treg cells of the signaling modulator CD5, the coinhibitors PD-1 and CTLA4, or the regulatory phosphatase DUSP4. However, transcriptome profiling in Dusp4-deficient mice showed that DUSP4 enhances the expression of a segment of the canonical Treg transcriptional signature, which partially overlaps with the TCR-dependent Treg gene set. Thus, Treg cells, likely because of their intrinsically higher reactivity to self, tune down TCR signals but seem comparatively more attuned to cytokines or other intercellular signals.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methanol, anhydrous, 99.8%
Sigma-Aldrich
Methanol, HPLC Plus, ≥99.9%, poly-coated bottles
Sigma-Aldrich
Methanol, suitable for HPLC, gradient grade, 99.93%
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
Sigma-Aldrich
Methanol, Laboratory Reagent, ≥99.6%
Sigma-Aldrich
Methanol, BioReagent, ≥99.93%
Sigma-Aldrich
Methanol, ACS spectrophotometric grade, ≥99.9%
Sigma-Aldrich
Interleukin-2 human, IL-2, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Sigma-Aldrich
Methanol, Absolute - Acetone free
Sigma-Aldrich
Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)
Sigma-Aldrich
IL-2 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
Interleukin-2 human, recombinant, expressed in Pichia pastoris, suitable for cell culture
Supelco
Methanol solution, contains 0.10 % (v/v) formic acid, UHPLC, suitable for mass spectrometry (MS), ≥99.5%
Sigma-Aldrich
Methanol, ACS reagent, ≥99.8%
Supelco
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 5 mm × 8 in.
Sigma-Aldrich
Interleukin-2 human, recombinant, expressed in E. coli, ~10000 U/mL
Sigma-Aldrich
Methanol, NMR reference standard
Sigma-Aldrich
Methanol solution, NMR reference standard, 4% in methanol-d4 (99.8 atom % D), NMR tube size 3 mm × 8 in.
Supelco
Methanol solution, contains 0.1 % (v/v) trifluoroacetic acid, 5 % (v/v) water, suitable for HPLC
Sigma-Aldrich
Methanol solution, (Methanol:Dimethyl sulfoxide 1:1 (v/v))
Sigma-Aldrich
Methanol-12C, 99.95 atom % 12C
Sigma-Aldrich
IL-2 human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE)