RT Journal Article
SR Electronic
T1 Inhibiting Oxidative Phosphorylation In Vivo Restrains Th17 Effector Responses and Ameliorates Murine Colitis
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 1600810
DO 10.4049/jimmunol.1600810
A1 Franchi, Luigi
A1 Monteleone, Ivan
A1 Hao, Ling-Yang
A1 Spahr, Mark A.
A1 Zhao, Wenpu
A1 Liu, Xikui
A1 Demock, Kellie
A1 Kulkarni, Aditi
A1 Lesch, Chuck A.
A1 Sanchez, Brian
A1 Carter, Laura
A1 Marafini, Irene
A1 Hu, Xiao
A1 Mashadova, Oksana
A1 Yuan, Min
A1 Asara, John M.
A1 Singh, Harinder
A1 Lyssiotis, Costas A.
A1 Monteleone, Giovanni
A1 Opipari, Anthony W.
A1 Glick, Gary D.
YR 2017
UL http://www.jimmunol.org/content/early/2017/02/24/jimmunol.1600810.abstract
AB Integration of signaling and metabolic pathways enables and sustains lymphocyte function. Whereas metabolic changes occurring during T cell activation are well characterized, the metabolic demands of differentiated T lymphocytes are largely unexplored. In this study, we defined the bioenergetics of Th17 effector cells generated in vivo. These cells depend on oxidative phosphorylation (OXPHOS) for energy and cytokine production. Mechanistically, the essential role of OXPHOS in Th17 cells results from their limited capacity to increase glycolysis in response to metabolic stresses. This metabolic program is observed in mouse and human Th17 cells, including those isolated from Crohn disease patients, and it is linked to disease, as inhibiting OXPHOS reduces the severity of murine colitis and psoriasis. These studies highlight the importance of analyzing metabolism in effector lymphocytes within in vivo inflammatory contexts and suggest a therapeutic role for manipulating OXPHOS in Th17-driven diseases.