FXR mediates T cell-intrinsic responses to reduced feeding during infection Journal Article
| Authors: | Campbell, C.; Marchildon, F.; Michaels, A. J.; Takemoto, N.; van der Veeken, J.; Schizas, M.; Pritykin, Y.; Leslie, C. S.; Intlekofer, A. M.; Cohen, P.; Rudensky, A. Y. |
| Article Title: | FXR mediates T cell-intrinsic responses to reduced feeding during infection |
| Abstract: | Reduced nutrient intake is a widely conserved manifestation of sickness behavior with poorly characterized effects on adaptive immune responses. During infectious challenges, naive T cells encountering their cognate antigen become activated and differentiate into highly proliferative effector T cells. Despite their evident metabolic shift upon activation, it remains unclear how effector T cells respond to changes in nutrient availability in vivo. Here, we show that spontaneous or imposed feeding reduction during infection decreases the numbers of splenic lymphocytes. Effector T cells showed cell-intrinsic responses dependent on the nuclear receptor Farnesoid X Receptor (FXR). Deletion of FXR in T cells prevented starvation-induced loss of lymphocytes and increased effector T cell fitness in nutrient-limiting conditions, but imparted greater weight loss to the host. FXR deficiency increased the contribution of glutamine and fatty acids toward respiration and enhanced cell survival under low-glucose conditions. Provision of glucose during anorexia of infection rescued effector T cells, suggesting that this sugar is a limiting nutrient for activated lymphocytes and that alternative fuel usage may affect cell survival in starved animals. Altogether, we identified a mechanism by which the host scales immune responses according to food intake, featuring FXR as a T cell-intrinsic sensor. Copyright © 2020 the Author(s). Published by PNAS. |
| Keywords: | anorexia; t cells; infection; fxr |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 117 |
| Issue: | 52 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2020-12-29 |
| Start Page: | 33446 |
| End Page: | 33454 |
| Language: | English |
| DOI: | 10.1073/pnas.2020619117 |
| PUBMED: | 33318189 |
| PROVIDER: | scopus |
| PMCID: | PMC7776647 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2021 -- Source: Scopus |
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