title: IL-7 modulates in vitro and in vivo human memory T regulatory cell functions through the CD39/ATP axis.
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.
authors: INSERM U955, Institut Mondor de Recherche Biomédicale, 94010 Créteil, France.
authors: Mehwish
authors: M
authors: Younas
authors: Sophie
authors: S
authors: Hue
authors: Christine
authors: C
authors: Lacabaratz
authors: Aurélie
authors: A
authors: Guguin
authors: Aurélie
authors: A
authors: Wiedemann
authors: Mathieu
authors: M
authors: Surenaud
authors: Stéphanie
authors: S
authors: Beq
authors: Thérèse
authors: T
authors: Croughs
authors: Jean-Daniel
authors: JD
authors: Lelièvre
authors: Yves
authors: Y
authors: Lévy
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology / Q000378:metabolism*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001081:Apyrase / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C508605:IL7 protein, human; D015851:Interleukin-7; D000255:Adenosine Triphosphate; D001081:Apyrase; C067869:CD39 antigen