Mitochondrial H2O2 in Lung Antigen-Presenting Cells Blocks NF-κB Activation to Prevent Unwarranted Immune Activation.
Publication/Presentation Date
5-24-2016
Abstract
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-κB, are not well understood. Here, we show that the nuclear receptor PPARγ plays a critical role in blocking NF-κB activation in response to inhaled antigens to preserve immune tolerance. Tolerance induction promoted mitochondrial respiration, generation of H2O2, and suppression of NF-κB activation in WT, but not PPARγ-deficient, APCs. Forced restoration of H2O2 in PPARγ-deficient cells suppressed IκBα degradation and NF-κB activation. Conversely, scavenging reactive oxygen species from mitochondria promoted IκBα degradation with loss of regulatory and promotion of inflammatory T cell responses in vivo. Thus, communication between PPARγ and the mitochondria maintains immune quiescence in the airways.
Volume
15
Issue
8
First Page
1700
Last Page
1714
ISSN
2211-1247
Published In/Presented At
Khare, A., Raundhal, M., Chakraborty, K., Das, S., Corey, C., Kamga, C. K., Quesnelle, K., St Croix, C., Watkins, S. C., Morse, C., Oriss, T. B., Huff, R., Hannum, R., Ray, P., Shiva, S., & Ray, A. (2016). Mitochondrial H2O2 in Lung Antigen-Presenting Cells Blocks NF-κB Activation to Prevent Unwarranted Immune Activation. Cell reports, 15(8), 1700–1714. https://doi.org/10.1016/j.celrep.2016.04.060
Disciplines
Medicine and Health Sciences
PubMedID
27184852
Department(s)
Department of Medicine
Document Type
Article