Presenting Author: Felipe Teixeira Lima
, Research Scholar/Postdoctoral Associate at Univ. of Florida
Abstract:
Introduction: The enzyme, MOF (males absent of the first), is a histone acetyltransferase that regulates the transcription of nuclear and mitochondrial genes. The role of MOF in acquired immunity has not been established.
Hypothesis: Expression of MOF controls CD4 T cell phenotype by regulating cellular metabolism.
Materials, Methods, and Results: We generated mice selectively deficient in MOF in CD4 T cells (Moff/f CD4cre). After ex vivo stimulation with CD3 and CD28, MOF-deficient splenic CD4 T cells displayed lower proliferation rate and viability, associated with altered mitochondrial morphology by electron microscopy, impaired oxidative phosphorylation, and higher glycolytic capacity, lactate production, and higher ATP production. In vivo, Moff/f CD4cre mice developed spontaneous rectal prolapse and colonic cryptitis. Intraepithelial and lamina propria CD4 T cell from these animals were disproportionately activated and displayed a Th17 phenotype. Treating these animals with a mitochondrion-targeted antioxidant, mitotempo, for a month resulted in normalization of T cell ATP production and lactate production.
Conclusion: The histone acetyltransferase MOF moderates T cell activation and polarization by controlling mitochondrial respiration, protecting against the spontaneous development of colitis.
Deletion of MOF in CD4 T cells results in mitochondrial dysfunction, Th17 polarization, and colonic inflammation.
Category
Poster and Podium (Block Symposium)
Description
Custom CSS
double-click to edit, do not edit in source
Date: May 5 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1