Plasticity of Treg and imbalance of Treg/Th17 cells in patients with systemic sclerosis modified by FK506.

To determine the effects of Tacrolimus (FK506) on Treg cells and subpopulations in SSc patients and assess the ability of FK506 to modify the immune imbalance of Treg/Th17 cells. We analyzed PBMC from five SSc patients and six healthy control by flow cytometry after cultured with 0, 0.1, 1, or 10 ng/ml FK506 in vitro. The number of Treg cells decreased in SSc patients treated with FK506. The number of FrI cells were decreased in SSc following FK506 treatment. The drug did increase the frequency of FrII/Treg cells, but not FrII cells. However, FK506 significantly decreased FrIII in both SSc patients and controls. FK506 clearly decreased the numbers of Th17 cells and FoxP3+IL-17+ cells. The proliferation capacity of cells was also inhibited by FK506, which had a greater effect on FoxP3- cells than FoxP3+ cells. FK506 did inhibit the proliferation of FrIII cells, but not FrI or FrII cells. Our study provides that FK506 reduced the number of FoxP3low CD45RA- T cells (FrIII) by inhibiting its proliferation. Therefore, FK506 modifies Treg cells and the immune imbalance between Tregs and Th17 cells in SSc patients.