| First Author | Dissanayake D | Year | 2011 |
| Journal | Nat Med | Volume | 17 |
| Issue | 12 | Pages | 1663-7 |
| PubMed ID | 22081022 | Mgi Jnum | J:180207 |
| Mgi Id | MGI:5305858 | Doi | 10.1038/nm.2556 |
| Citation | Dissanayake D, et al. (2011) Nuclear factor-kappaB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells. Nat Med 17(12):1663-7 |
| abstractText | Mature dendritic cells (DCs) are crucial for the induction of adaptive immune responses and perturbed DC homeostasis can result in autoimmune disease. Either uncontrolled expansion or enhanced survival of DCs can result in a variety of autoimmune diseases in mouse models. In addition, increased maturation signals, through overexpression of surface Toll-like receptors (TLRs) or stimulation by type I interferon (IFN), has been associated with systemic autoimmunity. Whereas recent studies have focused on identifying factors required for initiating the maturation process, the possibility that resting DCs also express molecules that 'hold' them in an immature state has generally not been considered. Here we show that nuclear factor-kappaB1 (NF-kappaB1) is crucial for maintaining the resting state of DCs. Self-antigen-pulsed unstimulated DCs that do not express NF-kappaB1 were able to activate CD8(+) T lymphocytes and induce autoimmunity. We further show that NF-kappaB1 negatively regulates the spontaneous production of tumor necrosis factor-alpha (TNF-alpha), which is associated with increased granzyme B expression in cytotoxic T lymphocytes (CTLs). These findings provide a new perspective on functional DC maturation and a potential mechanism that may account for pathologic T cell activation. |
