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IL-17 cytokines preferentially act on naïve CD4+ T cells with the IL-17AF heterodimer inducing the greatest functional changes
Journal article   Open access   Peer reviewed

IL-17 cytokines preferentially act on naïve CD4+ T cells with the IL-17AF heterodimer inducing the greatest functional changes

Michael P Crawford, Nicholas Borcherding and Nitin J Karandikar
PloS one, Vol.18(4), e0285166
2023
DOI: 10.1371/journal.pone.0285166
PMCID: PMC10146571
PMID: 37115755
url
https://doi.org/10.1371/journal.pone.0285166View
Published (Version of record) Open Access

Abstract

CD4+ T-helper 17 (Th17) T cells are a key population in protective immunity during infection and in self-tolerance/autoimmunity. Through the secretion of IL-17, Th17 cells act in promotion of inflammation and are thus a major potential therapeutic target in autoimmune disorders. Recent reports have brought to light that the IL-17 family cytokines, IL-17A, IL-17F and IL-17AF, can directly act on CD4+ T-cells, both in murine and human systems, inducing functional changes in these cells. Here we show that this action is preferentially targeted toward naïve, but not memory, CD4+ T-cells. Naïve cells showed transcriptome changes as early as 48 hours post-IL-17 exposure, whereas memory cells remained unaffected as late as 7 days. These functional differences occurred despite similar IL-17 receptor expression on these subsets and were maintained in co-culture/transwell systems, with each subset maintaining its functional response to IL-17. Importantly, there were differences in downstream transcriptional signaling by the three IL-17 cytokines, with the IL-17AF heterodimer conferring both the greatest transcriptional change and most altered functional consequences. Detailed transcriptome analysis provides important insights into the genes and pathways that are modulated as a result of IL-17-mediated signaling and may serve as targets of future therapies.

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