Effector T-cell subsets in systemic lupus erythematosus: update focusing on Th17 cells

The discovery of T helper (Th)17 cells that produce the proinflammatory cytokine IL-17 has substantially advanced our understanding of T-cell biology and autoimmunity. We will review recent findings on effector T cells, in particular Th17 cells, in lupus.

Studies reported increased IL-17 levels in the circulation and tissues in human and murine lupus. Patients with systemic lupus erythematosus (SLE or lupus) had an increased frequency of Th17 cells in peripheral blood which correlated with disease activity. However, the frequency of IFN-γ-producing Th1 cells did not change in the same patients, suggesting a selective dysregulation of Th17 cells in SLE. In addition, patients with SLE had an increased frequency of IL-17-producing CD3CD4CD8 (double negative) T cells in the peripheral blood and kidneys. Similar findings were noticed in lupus-prone MRL/MP-lpr/lpr (MRL/lpr) mice. A recent study demonstrated that IL-17 could promote B-cell survival and differentiation into antibody-producing cells. This raises the possibility that IL-17 is implicated in the pathogenesis of SLE by promoting humoral immunity against self-antigen.

Emerging data show a body of evidence that IL-17 and Th17 cells may play a role in the pathogenesis of SLE. Further studies are warranted to dissect the mechanism for increased IL-17 production and the therapeutic implication of targeting this cytokine in SLE.