Mitochondrial H2O2 in Lung Antigen-Presenting Cells Blocks NF-kappa B Activation to Prevent Unwarranted Immune Activation

作者：Khare Anupriya; Raundhal Mahesh; Chakraborty Krishnendu; Das Sudipta; Corey Catherine; Kamga Christelle K; Quesnelle Kelly; St Croix Claudette; Watkins Simon C; Morse Christina; Oriss Timothy B; Huff Rachael; Hannum Rachel; Ray Prabir; Shiva Sruti; Ray Anuradha^*

来源：Cell Reports, 2016, 15(8): 1700-1714.

DOI：10.1016/j.celrep.2016.04.060

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-kappa B, are not well understood. Here, we show that the nuclear receptor PPAR gamma plays a critical role in blocking NF-kappa B activation in response to inhaled antigens to preserve immune tolerance. Tolerance induction promoted mitochondrial respiration, generation of H2O2, and suppression of NF kappa B activation in WT, but not PPAR gamma-deficient, APCs. Forced restoration of H2O2 in PPAR gamma-deficient cells suppressed I kappa B alpha degradation and NF-kappa B activation. Conversely, scavenging reactive oxygen species from mitochondria promoted I kappa B alpha degradation with loss of regulatory and promotion of inflammatory T cell responses in vivo. Thus, communication between PPAR gamma and the mitochondria maintains immune quiescence in the airways.

• 出版日期2016-5-24