1. mTORC1 signaling in antigen-presenting cells of the skin restrains CD8 + T cell priming.
- Author
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Pelgrom LR, Patente TA, Otto F, Nouwen LV, Ozir-Fazalalikhan A, van der Ham AJ, van der Zande HJP, Heieis GA, Arens R, and Everts B
- Subjects
- Animals, Langerhans Cells immunology, Langerhans Cells metabolism, Mice, Signal Transduction, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Mechanistic Target of Rapamycin Complex 1 metabolism, Skin immunology, Skin metabolism
- Abstract
How mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of cellular metabolism, affects dendritic cell (DC) metabolism and T cell-priming capacity has primarily been investigated in vitro, but how mTORC1 regulates this in vivo remains poorly defined. Here, using mice deficient for mTORC1 component raptor in DCs, we find that loss of mTORC1 negatively affects glycolytic and fatty acid metabolism and maturation of conventional DCs, particularly cDC1s. Nonetheless, antigen-specific CD8
+ T cell responses to infection are not compromised and are even enhanced following skin immunization. This is associated with increased activation of Langerhans cells and a subpopulation of EpCAM-expressing cDC1s, of which the latter show an increased physical interaction with CD8+ T cells in situ. Together, this work reveals that mTORC1 limits CD8+ T cell priming in vivo by differentially orchestrating the metabolism and immunogenicity of distinct antigen-presenting cell subsets, which may have implications for clinical use of mTOR inhibitors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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