| First Author | Khare A | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 8 | Pages | 1700-14 |
| PubMed ID | 27184852 | Mgi Jnum | J:235753 |
| Mgi Id | MGI:5800625 | Doi | 10.1016/j.celrep.2016.04.060 |
| Citation | Khare A, et al. (2016) Mitochondrial H2O2 in Lung Antigen-Presenting Cells Blocks NF-kappaB Activation to Prevent Unwarranted Immune Activation. Cell Rep 15(8):1700-14 |
| abstractText | Inhalation of environmental antigens such as allergens does not always induce inflammation in the respiratory tract. While antigen-presenting cells (APCs), including dendritic cells and macrophages, take up inhaled antigens, the cell-intrinsic molecular mechanisms that prevent an inflammatory response during this process, such as activation of the transcription factor NF-kappaB, are not well understood. Here, we show that the nuclear receptor PPARgamma plays a critical role in blocking NF-kappaB activation in response to inhaled antigens to preserve immune tolerance. Tolerance induction promoted mitochondrial respiration, generation of H2O2, and suppression of NF-kappaB activation in WT, but not PPARgamma-deficient, APCs. Forced restoration of H2O2 in PPARgamma-deficient cells suppressed IkappaBalpha degradation and NF-kappaB activation. Conversely, scavenging reactive oxygen species from mitochondria promoted IkappaBalpha degradation with loss of regulatory and promotion of inflammatory T cell responses in vivo. Thus, communication between PPARgamma and the mitochondria maintains immune quiescence in the airways. |
