Abnormal activation of the Akt-GSK3beta signaling pathway in peripheral blood T cells from patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease accompanied by the activation and proliferation of T cells and B cells. In this study, we found that the distributions of lymphocytes obtained from patients with SLE or SLE with renal disease (RSLE) were reduced in the G(0)/G(1) phase and were elevated in the S phase after phytohemagglutinin treatment. Increased expression of CDK2 and decreased expression of cyclin-dependent kinase inhibitors p27(Kip1) and p21(WAF1/CIP1) were observed in RSLE and SLE lymphocytes. The phosphorylation levels of Akt473 and GSK3beta (ser9) were increased in lymphocytes from the patients. Moreover, inhibition of GSK3beta with lithium chloride or SB216763 induced T cell proliferation, and the most significant effects were observed in RSLE lymphocytes. These results indicate that upregulation of CDKs and downregulation of p27(Kip1) and p21(WAF1/CIP1) increased the proliferation of T lymphocytes in SLE patients. Abnormal activation of the Akt-GSK3beta signaling pathway increased the proliferation of lupus lymphocytes.