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  • IL-7 modulates in vitro and in vivo human memory T regulatory cell functions through the CD39/ATP axis.

IL-7 modulates in vitro and in vivo human memory T regulatory cell functions through the CD39/ATP axis.

Journal of immunology (Baltimore, Md. : 1950) (2013-08-24)
Mehwish Younas, Sophie Hue, Christine Lacabaratz, Aurélie Guguin, Aurélie Wiedemann, Mathieu Surenaud, Stéphanie Beq, Thérèse Croughs, Jean-Daniel Lelièvre, Yves Lévy
ABSTRACT

The heterogeneity of human regulatory T cells (Tregs) may explain the discrepancies between studies on Tregs in physiology and pathology. Contrasting effects of IL-7 on the expansion and survival of human Tregs were reported. Therefore, we investigated the effects of IL-7 on the phenotype and function of well-characterized populations of human Tregs. We show that IL-7 signals via the CD127 receptor on naive, memory, and activated memory Tregs sorted from the blood of healthy donors, but it does not affect their proliferation. In contrast, IL-7 affects their suppressive capacities differently. This effect was modest on naive Tregs but was dramatic (90%) on memory Tregs. We provide evidence that IL-7 exerts a synergistic effect through downmodulation of the ectoenzyme CD39, which converts ATP to ADP/AMP, and an increase in ATP receptor P2X7. Both effects lead to an increase in the ATP-mediated effect, tipping the balance to favor Th17 conversion. Using an IL-7 therapeutic study, we show that IL-7 exerts the same effects in vitro and in vivo in HIV-infected individuals. Globally, our data show that IL-7 negatively regulates Tregs and contributes to increase the number of tools that may affect Treg function in pathology.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Apyrase from potatoes, High Activity, ATPase ≥600 units/mg protein, lyophilized powder
Sigma-Aldrich
Apyrase from potatoes, ATPase ≥3.0 units/mg protein, lyophilized powder
Sigma-Aldrich
Apyrase from potatoes, ATPase ≥60 units/mg protein, lyophilized powder (partially purified)
Sigma-Aldrich
Apyrase from potatoes, ATPase ≥200 units/mg protein, lyophilized powder
Sigma-Aldrich
Apyrase from potatoes, ATPase ≥200 units/mg protein, lyophilized powder
Sigma-Aldrich
Apyrase from potato, recombinant, expressed in Pichia pastoris, ATPase ≥1000 units/mg protein, lyophilized powder