Karine SERRE, PhD

IMMUNOLOGIST

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IL-7 promotes IL-17-producing γδ T cells

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Here is, published :], the story that Marie-Laure Michel, from Hayday’s lab, presented at the 5th γδ T cell conference in Freiburg earlier this year.

She demonstrates the importance of IL-7 in expanding IL-17-producing CD27- γδ T cells in vitro and in vivo.

Administration of recombinant IL-7 three times over 5 days leads to an enrichment of CD44hi γδ27− cells over fivefold, compared with two- to threefold increases in IFN-γ–competent CD44low γδ27+ cells. Most interestingly, IL-7 is also required in vivo during acute psoriasis lesion formation (which is highly dependent on IL-17–producing γδ cells in the skin and skin-draining LN). Indeed, injection of anti–IL-7R antibody almost completely blocked the enrichment (~10-fold) in IL-17+ γδ cells in the skin draining LN of mice administered imiquimod.

Importantly, IL-7 does not induce de novo conversion of γδ T cells into IL-17-producing cells but rather expands cells with the property to secrete IL-17. Although, CD27- γδ T cells are viewed as innate cells because they rapidly respond to IL-23 + IL-1β, they show here that IL-7 synergizes with TCR ligation to trigger expansion, activation markers, or effector function.

Furthermore, this is not an epiphenomenon observed uniquely with murine cells as this also applies to human IL-17 producing cells (and in particular derived from cord-blood) through a similar signaling pathway!! This is an important result because, by contrast to mice, a substantial subset of IL-17–producing human γδ T cells has been hard to identify in healthy donors so far.

Finally, it is critical to compare signaling pathways and consequences between γδ27- cells and conventional Th17 cells. It is striking that IL-7 also as positive influence on Th17 cells. However, surprisingly, while IL-7 signals through STAT3 in γδ27- it signals through STAT5 in Th17 cells.

Here is the pubmed link: IL-7 positively increases the generation of IL-17-producing γδ cells.

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