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

Abstract 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 favor...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.) Fla.), 2014-04, Vol.151 (2), p.136-145
Hauptverfasser: Boks, Martine A, Kager-Groenland, Judith R, Mousset, Charlotte M, van Ham, S. Marieke, ten Brinke, Anja
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Sprache:eng
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Zusammenfassung:Abstract 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 affected sustained T cell differentiation in later stages of T cell priming. Whole genome gene expression analysis revealed an extended regulatory gene profile for anti-TNFα-treated T cells. Indeed, neutralizing TNFα during naïve T cell priming enhanced the suppressive function of anti-TNFα-treated T cells. Taken together, inhibition of TNFα–TNFR interaction shifts the balance of Th cell differentiation towards IL-10 expressing suppressive T cells, which may be one of the beneficial mechanisms in TNFα blocking therapies.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2014.02.008