MTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation

Charles Sinclair; Gayathri Bommakanti; Luiz Gardinassi; Jens Loebbermann; Matthew Joseph Johnson; Paul Hakimpour; Thomas Hagan; Lydia Benitez; Andrei Todor; Deepa Machiah; Timothy Oriss; Anuradha Ray; Steven Bosinger; Rajesh Ravindran; Shuzhao Li; Bali Pulendran

doi:10.1126/science.aaj2155

MTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation

Charles Sinclair, Gayathri Bommakanti, Luiz Gardinassi, Jens Loebbermann, Matthew Joseph Johnson, Paul Hakimpour, Thomas Hagan, Lydia Benitez, Andrei Todor, Deepa Machiah, Timothy Oriss, Anuradha Ray, Steven Bosinger, Rajesh Ravindran, Shuzhao Li, Bali Pulendran

Genetics, Cell Biology and Development (TMED)

Research output: Contribution to journal › Article › peer-review

89 Scopus citations

Abstract

Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissuerestricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103⁺ DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b⁺ DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T_H2) to neutrophilic T_H17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.

Original language	English (US)
Pages (from-to)	1014-1021
Number of pages	8
Journal	Science
Volume	357
Issue number	6355
DOIs	https://doi.org/10.1126/science.aaj2155
State	Published - Sep 8 2017

Bibliographical note

Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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10.1126/science.aaj2155

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746055

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Sinclair, C., Bommakanti, G., Gardinassi, L., Loebbermann, J., Johnson, M. J., Hakimpour, P., Hagan, T., Benitez, L., Todor, A., Machiah, D., Oriss, T., Ray, A., Bosinger, S., Ravindran, R., Li, S., & Pulendran, B. (2017). MTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation. Science, 357(6355), 1014-1021. https://doi.org/10.1126/science.aaj2155

Sinclair, C, Bommakanti, G, Gardinassi, L, Loebbermann, J, Johnson, MJ, Hakimpour, P, Hagan, T, Benitez, L, Todor, A, Machiah, D, Oriss, T, Ray, A, Bosinger, S, Ravindran, R, Li, S & Pulendran, B 2017, 'MTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation', Science, vol. 357, no. 6355, pp. 1014-1021. https://doi.org/10.1126/science.aaj2155

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abstract = "Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissuerestricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)-dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103+ DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b+ DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (TH2) to neutrophilic TH17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.",

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AU - Johnson, Matthew Joseph

AU - Hakimpour, Paul

AU - Hagan, Thomas

AU - Benitez, Lydia

AU - Todor, Andrei

AU - Machiah, Deepa

AU - Oriss, Timothy

AU - Ray, Anuradha

AU - Bosinger, Steven

AU - Ravindran, Rajesh

AU - Li, Shuzhao

AU - Pulendran, Bali

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MTOR regulates metabolic adaptation of APCs in the lung and controls the outcome of allergic inflammation

Abstract

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