Unraveling the identity of FoxP3+ regulatory T cells in Granulomatosis with Polyangiitis patients.

ABSTRACT: Human CD4⁺FoxP3⁺T-cells are heterogeneous in function and include not only suppressive cells (Tregs), but also effector cells that transiently express FoxP3 upon activation. Previous studies in Granulomatosis with Polyangiitis (GPA-)patients have demonstrated an increase in FoxP3⁺T-cells with impaired suppressive capacity and an increase in Th17 cells. We hypothesized that the increase in FoxP3⁺T-cells results from an increase in non-suppressive effector-like cells. The frequency of circulating CD4⁺FoxP3⁺T-cell subsets were determined by flow cytometry in 46 GPA-patients in remission and 22 matched healthy controls (HCs). Expression levels of FoxP3 and CD45RO were used to distinguish between CD45RO^- FoxP3^low resting Tregs (rTreg), CD45RO⁺FoxP3^high activated Tregs (aTreg) and CD45RO⁺FoxP3^low proinflammatory non-suppressive T-cells (nonTreg). Intracellular expression of IFNγ, IL-17, and IL-21 was compared within these subsets. We found a significant increase in the frequency of nonTreg cells in GPA-patients as compared with HCs. Importantly, within the nonTreg subset, antineutrophil cytoplasmic autoantibody (ANCA-)positive patients demonstrated a significantly higher percentage of IL-17+ and IL-21+ cells when compared with ANCA-negative patients and HCs. Moreover, expanded nonTregs from ANCA-positive patients induced excessive proliferation of responder cells in vitro and exhibited higher IL-21 production. Production of IL-17 and IL-21 in non-suppressive FoxP3⁺T-cells may point toward a pathogenic role in ANCA formation.

SUBMITTER: Reijnders TDY 

PROVIDER: S-EPMC6547679 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature