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.

Franchi, L., Monteleone, I., Hao, L., Spahr, M.a., Zhao, W., Liu, X., et al. (2017). Inhibiting Oxidative Phosphorylation In Vivo Restrains Th17 Effector Responses and Ameliorates Murine Colitis. JOURNAL OF IMMUNOLOGY, 198(7), 2735-2746 [10.4049/jimmunol.1600810].

Inhibiting Oxidative Phosphorylation In Vivo Restrains Th17 Effector Responses and Ameliorates Murine Colitis

MONTELEONE, IVAN;MARAFINI, IRENE;MONTELEONE, GIOVANNI;
2017

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/12 - Gastroenterologia
English
Franchi, L., Monteleone, I., Hao, L., Spahr, M.a., Zhao, W., Liu, X., et al. (2017). Inhibiting Oxidative Phosphorylation In Vivo Restrains Th17 Effector Responses and Ameliorates Murine Colitis. JOURNAL OF IMMUNOLOGY, 198(7), 2735-2746 [10.4049/jimmunol.1600810].
Franchi, L; Monteleone, I; Hao, L; Spahr, M; Zhao, W; Liu, X; Demock, K; Kulkarni, A; Lesch, C; Sanchez, B; Carter, L; Marafini, I; Hu, X; Mashadova, O; Yuan, M; Asara, J; Singh, H; Lyssiotis, C; Monteleone, G; Opipari, A; Glick, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/174712
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