Progranulin Inhibits Human T Lymphocyte Proliferation by Inducing the Formation of Regulatory T Lymphocytes

Figure 3

PGRN exerts its inhibitory effect by inducing the conversion of CD4⁺ T lymphocytes to iTregs via TGF-β. CD4⁺ T lymphocytes were stimulated with PHA and incubated with PGRN in the presence or absence of 1, 10, and 20 μM of TGF-β inhibitor for 5 days (a). CD4⁺ T lymphocytes were stimulated with PHA and incubated with PGRN in the presence or absence of 1, 10, and 25 μg/ml of Treg inhibitor for 5 days (b). Treated cells were collected and divided into two; one lot was stained for iTregs and the other was analyzed by cell proliferation assay. Flow cytometry was performed to determine iTregs and the proportion of iTregs. Upper panels in show the percentage of CD4⁺ T lymphocytes incorporated with EdU. Lower panels show the percentage of CD4⁺Foxp3⁺ iTreg ((a) and (b)). Data are presented as means ± standard deviations of three experiments performed in triplicate. , , or ns (not significant). Similar results were obtained in three independent experiments.

(a)

(b)