PD-1 deletion restores susceptibility to experimental autoimmune encephalomyelitis in miR-155-deficient mice

MiR-155 –/– mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), while Pdcd1 –/– mice develop a more severe form of the disease. To determine the conflicting roles of these two molecules in the disease, we generated miR-155 –/– Pdcd1 –/– double knockout (DKO) mice. We found that ablation of programmed cell death protein 1 (PD-1) expression in miR-155-deficient mice restored the susceptibility to EAE. The increased severity of the disease in DKO mice was accompanied by an enhanced T-cell infiltration into the brain as well as an increased production of pro-inflammatory cytokines IFN- and IL-17. Furthermore, the major contribution of the DKO to EAE was T-cell intrinsic since adoptive transfer of CD4+ T cells from DKO donors promoted the disease in lymphopenic recipients. These results define PD-1 deficiency in miR-155 –/– mice as a promoting factor of autoimmune inflammation by increasing antigen-driven T-cell expansion and infiltration.

Source: International Immunology - June 30, 2014 Category: Allergy & Immunology Authors: Zhang, J., Braun, M. Y. Tags: Original Research Source Type: research