SHPS-1 positively regulates T cell priming and cytokine production by dendritic cells (DCs). (89.15)

Abstract

Abstract [Background] SHPS-1, a transmembrane protein that binds protein tyrosine phosphatases in its cytoplasmic region, is predominantly expressed on DCs, but the role of SHPS-1 signals during T cell priming by DCs is largely unknown. Here, we investigated the physiological roles of SHPS-1 in the functions of DCs by the use of SHPS-1 mutant mice, which lack most of the cytoplasmic region of this protein. [Methods] DCs were prepared from spleens by Auto MACS. The expression of SHPS-1 or costimulatory molecules on DCs were examined by FCM. IL-12-induced IFN-γ production by DCs was determined by ELISA. The ability of DCs for antigen presentation was evaluated by the incubation of OT-II cells with OVA-loaded DCs. [Results] FCM analysis showed that SHPS-1 was predominantily expressed on CD8α− DCs. The expression level of SHPS-1 was reduced in DCs from SHPS-1 mutant mice, but the expression levels of costimulatory molecules on DCs from SHPS-1 mutant mice were almost comparable to that on WT DCs. On the contrary, IL-12-induced production of IFN-γ was reduced in DCs from SHPS-1 mutant mice. The ability of DCs to stimulate proliferation of OVA-specific CD4+ T cells was also impaired in DCs from SHPS-1 mutant mice. [Conclusion] SHPS-1 positively regulates DC functions including CD4+ T cell priming and cytokine production.