Transcriptomics

Dataset Information

2

CD4+ T cells treated with TNFalpha blocking agents during activation.


ABSTRACT: Objective. TNFα is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Neutralizing TNFα inhibits T cell proliferation and IFNγ production, and enhances suppressive capacity of regulatory T cells (Treg). Little is known about the mechanism of TNFα blocking agents on naïve T cell differentiation. Methods. Naïve CD4+ T cells were activated by dendritic cells (DC) in presence or absence of anti-TNFα agents. T cell polarization and activation was assessed during T cell differentiation. In addition, whole genome gene expression analysis was performed on anti-TNFα-treated T cells. Results. Neutralizing TNFα during priming of naïve CD4+ T cells by DC favors development of IL-10+ T helper (Th) cells at the expense of IFNγ induction. TNFα inhibits IL-10 via TNFRII, which becomes expressed after naïve T cell activation. While initial CD4+ T cell activation was not affected, neutralization of TNFα negatively affected later stages of T cell priming by counteracting full T cell activation and survival. Whole genome gene expression analysis revealed a regulatory gene profile of anti-TNFα-treated T cells. Indeed, neutralizing TNFα during naïve T cell priming enhanced the suppressive function of anti-TNFα-treated T cells. Conclusion. Inhibition of TNFα–TNFRII interaction affects late stage effector T cell development and shifts the balance of Th cell differentiation towards IL-10 expressing regulatory T cells, which may be one of the beneficial mechanisms in TNFα blocking therapies. Naïve CD4+ T cells were CFSE labeled and co-cultured for 13 days with allogeneic dendritic cells in the presence or absence of anti-TNFα agents. After 13 days, the CFSElow T cells were FACS sorted. Samples were generated from three independent donors.

ORGANISM(S): Homo sapiens  

SUBMITTER: Martine A Boks   Marieke van Ham  Martine A. Boks  Judith R Kager-Groenland  Anja ten Brinke 

PROVIDER: E-GEOD-42812 | ArrayExpress | 2014-06-25

SECONDARY ACCESSION(S): GSE42812PRJNA183430

REPOSITORIES: GEO, ArrayExpress

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Publications

Inhibition of TNF receptor signaling by anti-TNFα biologicals primes naïve CD4(+) T cells towards IL-10(+) T cells with a regulatory phenotype and function.

Boks Martine A MA   Kager-Groenland Judith R JR   Mousset Charlotte M CM   van Ham S Marieke SM   ten Brinke Anja A  

Clinical immunology (Orlando, Fla.) 20140222 2


TNFα is a potent pro-inflammatory cytokine playing a pivotal role in several autoimmune diseases. Little is known about the mechanism of TNFα blocking agents on naïve T cell differentiation. Here, we report that neutralizing TNFα during priming of naïve CD4(+) T cells by dendritic cells favors development of IL-10(+) T helper cells. TNFα counteracts IL-10(+) T cell priming mainly via TNFRI receptor signaling. While initial T cell activation was not affected, neutralization of TNFα negatively aff  ...[more]

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