First Author | Zhang J | Year | 2014 |
Journal | Int Immunol | Volume | 26 |
Issue | 7 | Pages | 407-15 |
PubMed ID | 24648472 | Mgi Jnum | J:331331 |
Mgi Id | MGI:6843514 | Doi | 10.1093/intimm/dxu043 |
Citation | Zhang J, et al. (2014) PD-1 deletion restores susceptibility to experimental autoimmune encephalomyelitis in miR-155-deficient mice. Int Immunol 26(7):407-15 |
abstractText | 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-gamma 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. |