| First Author | Haynes LD | Year | 2015 |
| Journal | J Immunol | Volume | 195 |
| Issue | 5 | Pages | 2157-67 |
| PubMed ID | 26232430 | Mgi Jnum | J:317767 |
| Mgi Id | MGI:6855889 | Doi | 10.4049/jimmunol.1402060 |
| Citation | Haynes LD, et al. (2015) Cardif (MAVS) Regulates the Maturation of NK Cells. J Immunol 195(5):2157-67 |
| abstractText | Cardif, also known as IPS-1, VISA, and MAVS, is an intracellular adaptor protein that functions downstream of the retinoic acid-inducible gene I family of pattern recognition receptors. Cardif is required for the production of type I IFNs and other inflammatory cytokines after retinoic acid-inducible gene I-like receptors recognize intracellular antigenic RNA. Studies have recently shown that Cardif may have other roles in the immune system in addition to its role in viral immunity. In this study, we find that the absence of Cardif alters normal NK cell development and maturation. Cardif(-/-) mice have a 35% loss of mature CD27(-)CD11b(+) NK cells in the periphery. In addition, Cardif(-/-) NK cells have altered surface marker expression, lower cytotoxicity, decreased intracellular STAT1 levels, increased apoptosis, and decreased proliferation compared with wild-type NK cells. Mixed chimeric mice revealed that the defective maturation and increased apoptotic rate of peripheral Cardif(-/-) NK cells is cell intrinsic. However, Cardif(-/-) mice showed enhanced control of mouse CMV (a DNA beta-herpesvirus) by NK cells, commensurate with increased activation and IFN-gamma production by these immature NK cell subsets. These results indicate that the skewed differentiation and altered STAT expression of Cardif(-/-) NK cells can result in their hyperresponsiveness in some settings and support recent findings that Cardif-dependent signaling can regulate aspects of immune cell development and/or function distinct from its well-characterized role in mediating cell-intrinsic defense to RNA viruses. |
