| First Author | Ellis GI | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 12 | Pages | 3355-60 |
| PubMed ID | 24037540 | Mgi Jnum | J:205923 |
| Mgi Id | MGI:5547435 | Doi | 10.1002/eji.201343571 |
| Citation | Ellis GI, et al. (2013) Mitochondrial and cytosolic roles of PINK1 shape induced regulatory T-cell development and function. Eur J Immunol 43(12):3355-60 |
| abstractText | Mutations in PTEN-induced kinase 1 (PINK1), a serine/threonine kinase linked to familial early-onset Parkinsonism, compromise mitochondrial integrity and metabolism and impair AKT signaling. As the activation of a naive T cell requires an AKT-dependent reorganization of a cell's metabolic machinery, we sought to determine if PINK1-deficient T cells lack the ability to undergo activation and differentiation. We show that CD4(+) T cells from PINK1 knockout mice fail to properly phosphorylate AKT upon activation, resulting in reduced expression of the IL-2 receptor subunit CD25. Following, deficient IL-2 signaling mutes the activation-induced increase in respiratory capacity and mitochondrial membrane potential. Under polarization conditions favoring the development of induced regulatory T cells, PINK1(-/-) T cells exhibit a reduced ability to suppress bystander T-cell proliferation despite normal FoxP3 expression kinetics. Our results describe a critical role for PINK1 in integrating extracellular signals with metabolic state during T-cell fate determination, and may have implications for the understanding of altered T-cell populations and immunity during the progression of active Parkinson's disease or other immunopathologies. |
