A truncated IL-12rβ1 receptor ameliorates chronic graft-versus-host disease-induced lupus nephritis by inhibiting Th1 and Th17 cells

Th1 and Th17 cells have been strongly implicated in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-12 and IL-23 respectively drive the polarization of Th1 and Th17 cells and share a common p40 subunit. In this study, the protective and therapeutic effects of a truncated human IL-12r beta 1 receptor (tIL12r beta 1) targeting IL-12/IL-23 p40 were evaluated in chronic graft-versus-host disease (cGVHD)-induced SLE-like model. The results indicated that tIL12r beta 1 treatment effectively delayed the proteinuria onset and induced a significant remission of proteinuria, autoantibody production, and immune complex deposition in the mouse model. Remarkably, the therapeutic effects of tIL12r beta 1 were predominantly dependent on the suppression of pathogenic Th1 and Th17 cell commitment through the reduction of ROR gamma t and T-bet expression. Collectively, this receptor molecule may offer a new treatment option for SLE. (C) 2015 Elsevier B.V. All rights reserved.