Combinatorial flexibility of cytokine function during human T helper cell differentiation

Maxime Touzot, Maximilien Grandclaudon, Antonio Cappuccio, Takeshi Satoh, Carolina Martinez-Cingolani, Nicolas Servant, Nicolas Manel and Vassili Soumelis ()
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Maxime Touzot: INSERM U932, 26 rue d’Ulm
Maximilien Grandclaudon: INSERM U932, 26 rue d’Ulm
Antonio Cappuccio: INSERM U932, 26 rue d’Ulm
Takeshi Satoh: INSERM U932, 26 rue d’Ulm
Carolina Martinez-Cingolani: INSERM U932, 26 rue d’Ulm
Nicolas Servant: Section Recherche, Institut Curie, 26 rue d’Ulm
Nicolas Manel: INSERM U932, 26 rue d’Ulm
Vassili Soumelis: INSERM U932, 26 rue d’Ulm

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: Abstract In an inflammatory microenvironment, multiple cytokines may act on the same target cell, creating the possibility for combinatorial interactions. How these may influence the system-level function of a given cytokine is unknown. Here we show that a single cytokine, interferon (IFN)-alpha, can generate multiple transcriptional signatures, including distinct functional modules of variable flexibility, when acting in four cytokine environments driving distinct T helper cell differentiation programs (Th0, Th1, Th2 and Th17). We provide experimental validation of a chemokine, cytokine and antiviral modules differentially induced by IFN-α in Th1, Th2 and Th17 environments. Functional impact is demonstrated for the antiviral response, with a lesser IFN-α-induced protection to HIV-1 and HIV-2 infection in a Th17 context. Our results reveal that a single cytokine can induce multiple transcriptional and functional programs in different microenvironments. This combinatorial flexibility creates a previously unrecognized diversity of responses, with potential impact on disease physiopathology and cytokine therapy.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4987

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DOI: 10.1038/ncomms4987

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